Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Phytochemicals and Nanoparticles in the Modulation of PI3K/Akt/mTOR Kinases and its Implications in the Development and Progression of Gastrointestinal Cancers: A Review of Preclinical and Clinical Evidence

Author(s): Arunaksharan Narayanankutty*, Sreelakshmi Nambiattil and Sreeshna Mannarakkal

Volume 18, Issue 3, 2023

Published on: 12 October, 2022

Page: [307 - 324] Pages: 18

DOI: 10.2174/1574892817666220606104712

Price: $65


Background: Gastrointestinal cancer are the major form of cancer in developing countries, which comprises gastric cancer (GC), hepatic cancer (HCC), colorectal cancers (CRC), etc.; they account for a large number of cancer-related deaths globally. Gastrointestinal cancers generally have a multifactorial origin, where both genetic and dietary factors play prominent roles. PI3K/Akt signaling is the prime signaling pathway associated with the Phosphoinositide-3 kinase/protein kinase B signaling pathway.

Objectives: The present review aims to summarize the role of the PI3K/Akt signaling pathway on the different events of gastrointestinal cancers, such as proliferation, survival, metastasis, angiogenesis, drug resistance and stem cell properties.

Methods: Literature collection has been done using the appropriate keywords from Pub- Med/Medline, Scopus, Web of science, or Eurekaselect. The details of individual types of cancers were selected by giving respective keywords.

Results: PI3K signaling pathway is important in various gastrointestinal carcinogenesis and progression events; the pathway is involved in proliferation, survival, metastasis, and drug resistance. Several natural phytochemicals and their derivatives have been shown to inhibit PI3K signaling and its downstream regulatory elements, subsequently resulting in anticancer and anti-metastatic activity. Although numerous preclinical evidences are available, conclusive clinical reports are lacking on the anticancer aspects of PI3K inhibitors in gastric cancer.

Conclusion: Phytochemicals are promising drug candidates for targeting the PI3K/mTOR pathway in various gastrointestinal cancer treatments. However, there is a need for extensive clinical studies to ascertain the commercial value of anticancer therapeutic compounds against cancers of the stomach, liver, and intestine.

Keywords: H Gastrointestinal cancer, PI3K/Akt signaling, phytochemicals, carcinogenesis, drug resistance, metastasis, colorectal cancer, gastric cancer, hepatocellular carcinoma.

Cassiman JJ. Is cancer a hereditary or a degenerative disease? Verh K Acad Geneeskd Belg 2001; 63(2): 137-52.
Engvild KC. Cancer follows chromosome missegregation when all endogenous repair mechanisms fail. Med Hypotheses 2018; 120: 121-3.
[ ] [PMID: 30220330]
Rew DA. Cancer--a degenerative disorder? Eur J Surg Oncol 1998; 24(5): 362-6.
[ ] [PMID: 9800960]
Brusselaers N, Lagergren J. Maintenance use of non-steroidal anti-inflammatory drugs and risk of gastrointestinal cancer in a nationwide population-based cohort study in Sweden. BMJ Open 2018; 8(7): e021869-9.
[ ] [PMID: 29982219]
Rawla P, Barsouk A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz Gastroenterol 2019; 14(1): 26-38.
[ ] [PMID: 30944675]
Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: Epidemiology, prevention, classification, and treatment. Cancer Manag Res 2018; 10: 239-48.
[ ] [PMID: 29445300]
Masami K, Noboru M. Plant-derived leading compounds for eradication of helicobacter pylori. Curr Med Anti Infect Agents 2004; 3(2): 89-100.
Luigiano C, Ferrara F, Fagoonee S. et al. Is Helicobacter pylori the infectious target to prevent gastric cancer? An interdisciplinary point of view. Infect Disord Drug Targets 2012; 12(5): 340-5.
[ ] [PMID: 23017162]
Sokolova O, Naumann M. NF-κB signaling in gastric cancer. Toxins (Basel) 2017; 9(4): 119.
[ ] [PMID: 28350359]
Narayanankutty V, Narayanankutty A, Nair A. Heat shock proteins (HSPs): A novel target for cancer metastasis prevention. Curr Drug Targets 2019; 20(7): 727-37.
[ ] [PMID: 30526455]
Narayanankutty A, Sasidharan A, Job JT. Targeting toll like receptors in Cancer: Role of TLR natural and synthetic modulators. Curr Pharm Des 2020; 26(39): 5040-53.E-pub Ahead of Print.
[ ] [PMID: 32693759]
Narayanankutty A. Toll-like receptors as a novel therapeutic target for natural products against chronic diseases. Curr Drug Targets 2019; 20(10): 1068-80.
[ ] [PMID: 30806312]
Magnelli L, Schiavone N, Staderini F, Biagioni A, Papucci L. MAP kinases pathways in gastric cancer. Int J Mol Sci 2020; 21(8): 2893.
[ ] [PMID: 32326163]
Gonzalez-Hormazabal P, Musleh M, Bustamante M. et al. Polymorphisms in RAS/RAF/MEK/ERK pathway are associated with gastric cancer. Genes (Basel) 2018; 10(1): 20.
[ ] [PMID: 30597917]
Chen M-B, Liu Y-Y, Cheng L-B, Lu J-W, Zeng P, Lu P-H. AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation. Oncotarget 2017; 8(19): 31288-96.
[ ] [PMID: 28423719]
Narayanankutty A. PI3K/ Akt/ mTOR pathway as a therapeutic target for colorectal cancer: A review of preclinical and clinical evidence. Curr Drug Targets 2019; 20(12): 1217-26.
[ ] [PMID: 31215384]
Narayanankutty A. Phytochemicals as PI3K/ Akt/ mTOR inhibitors and their role in breast cancer treatment. Recent Patents Anticancer Drug Discov 2020; 15(3): 188-99.
[ ] [PMID: 32914720]
Fattahi S, Amjadi-Moheb F, Tabaripour R, Ashrafi GH, Akhavan-Niaki H. PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond. Life Sci 2020; 262: 118513.
[ ] [PMID: 33011222]
Samuels Y, Ericson K. Oncogenic PI3K and its role in cancer. Curr Opin Oncol 2006; 18(1): 77-82.
[ ] [PMID: 16357568]
Roy HK, Olusola BF, Clemens DL. et al. AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis 2002; 23(1): 201-5.
[ ] [PMID: 11756242]
Du J, Yang M, Chen S, Li D, Chang Z, Dong Z. PDK1 promotes tumor growth and metastasis in a spontaneous breast cancer model. Oncogene 2016; 35(25): 3314-23.
[ ] [PMID: 26455327]
Yecies JL, Manning BD. mTOR links oncogenic signaling to tumor cell metabolism. J Mol Med (Berl) 2011; 89(3): 221-8.
[ ] [PMID: 21301797]
Luongo F, Colonna F, Calapà F, Vitale S, Fiori ME, De Maria R. PTEN tumor-suppressor: The dam of stemness in Cancer. Cancers (Basel) 2019; 11(8): 1076
[] [PMID: 31366089]
Zhang Y, Chen P, Yin W, Ji Y, Shen Q, Ni Q. Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway. Hum Pathol 2018; 72: 107-16.
[ ] [PMID: 29208564]
Xu J, Gong L, Qian Z, Song G, Liu J. ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncol Rep 2018; 39(6): 2892-8.
[ ] [PMID: 29620274]
Qu H, Sun H, Wang X. Neogenin-1 promotes cell proliferation, motility, and adhesion by up-regulation of zinc finger E-box binding homeobox 1 via activating the Rac1/PI3K/AKT pathway in gastric cancer cells. Cellular physiology and biochemistr: International journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 48(4): 1457-67.
Qiu YS, Liao GJ, Jiang NN. REG3A overexpression suppresses gastric cancer cell invasion, proliferation and promotes apoptosis through PI3K/Akt signaling pathway. Int J Mol Med 2018; 41(6): 3167-74.
[ ] [PMID: 29512686]
Ke J, Ma P, Chen J, Qin J, Qian H. LGR6 promotes the progression of gastric cancer through PI3K/AKT/mTOR pathway. OncoTargets Ther 2018; 11: 3025-33.
[ ] [PMID: 29872314]
Zhao H, Xu J, Wang Y. et al. Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of PI3K/Akt and NF-κB. Surg Oncol 2018; 27(3): 495-502.
[ ] [PMID: 30217308]
Zang M, Zhang B, Zhang Y. et al. CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PLoS One 2014; 9(11): e112908.
[ ] [PMID: 25398131]
Li C, Zhang J, Wu H. et al. Lectin-like oxidized low-density lipoprotein receptor-1 facilitates metastasis of gastric cancer through driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation. Sci Rep 2017; 7(1): 45275.
[ ] [PMID: 28345638]
Diao L, Li Y, Mei Q, Han W, Hu J. AIB1 induces epithelial-mesenchymal transition in gastric cancer via the PI3K/AKT signaling. J Cell Biochem 2019.
[PMID: 31692102]
Song SZ, Lin S, Liu JN. et al. Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial-mesenchymal transition through inhibition of the PI3K/AKT signaling pathway. J Cell Physiol 2019; 234(10): 18587-601.
[ ] [PMID: 30953349]
Lu WD, Zuo Y, Xu Z, Zhang M. MiR-19a promotes epithelialmesenchymal transition through PI3K/AKT pathway in gastric cancer. World J Gastroenterol 2015; 21(15): 4564-73.
[ ] [PMID: 25914465]
Lv WL, Hu YY, Li ZN, Zhang W, Pan Q. PAX3 silencing suppresses gastric cancer proliferation and angiogenesis via MET/PI3K signaling. Neoplasma 2020; 67(2): 304-11.
[ ] [PMID: 31847528]
Xing X, Zhang L, Wen X. et al. PP242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway. Anticancer Drugs 2014; 25(10): 1129-40.
[ ] [PMID: 25035961]
Peng X, Zhou J, Li B, Zhang T, Zuo Y, Gu X. Notch1 and PI3K/Akt signaling blockers DAPT and LY294002 coordinately inhibit metastasis of gastric cancer through mutual enhancement. Cancer Chemother Pharmacol 2020; 85(2): 309-20.
[ ] [PMID: 31732769]
Huang Z, Liang H, Chen L. RAB43 Promotes Gastric Cancer Cell Proliferation and Metastasis via Regulating the PI3K/AKT Signaling Pathway. OncoTargets Ther 2020; 13: 2193-202.
[ ] [PMID: 32210585]
Shi L, Wu Z, Miao J. et al. Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K-AKT-mTOR signaling. Mol Biol Cell 2019; 30(19): 2527-34.
[ ] [PMID: 31339445]
Hao NB, Tang B, Wang GZ. et al. Hepatocyte growth factor (HGF) upregulates heparanase expression via the PI3K/Akt/NF-κB signaling pathway for gastric cancer metastasis. Cancer Lett 2015; 361(1): 57-66.
[ ] [PMID: 25727320]
Liu L, Ye Y, Zhu X. MMP-9 secreted by tumor associated macrophages promoted gastric cancer metastasis through a PI3K/AKT/Snail pathway. Biomed Pharmacothe 2019; 117: 109096.
Zhang Y, Li Z, Fan X. et al. PRL-3 promotes gastric cancer peritoneal metastasis via the PI3K/AKT signaling pathway in vitro and in vivo. Oncol Lett 2018; 15(6): 9069-74.
[ ] [PMID: 29805638]
Xiong J, Li Z, Zhang Y. et al. PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncol Rep 2016; 36(4): 1819-28.
[ ] [PMID: 27572739]
Liu JY, Jiang L, He T. et al. NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients. Cell Death Dis 2019; 10(3): 162.
[ ] [PMID: 30770791]
Sun C, Tao Y, Gao Y. et al. F-box protein 11 promotes the growth and metastasis of gastric cancer via PI3K/AKT pathway-mediated EMT. Biomed Pharmacothe 2018; 98: 416-23.
Wei S, Wang L, Zhang L. et al. ZNF143 enhances metastasis of gastric cancer by promoting the process of EMT through PI3K/AKT signaling pathway. Tumour Biol 2016; 37(9): 12813-21.
[ ] [PMID: 27449034]
Ji N, Yu JW, Ni XC, Wu JG, Wang SL, Jiang BJ. Bone marrowderived mesenchymal stem cells increase drug resistance in CD133-expressing gastric cancer cells by regulating the PI3K/AKT pathway. Tumour Biol 2016; 37(11): 14637-51.
[ ] [PMID: 27619680]
Song S, Pei G, Du Y. et al. Interaction between CD133 and PI3Kp85 promotes chemoresistance in gastric cancer cells. Am J Transl Res 2018; 10(1): 304-14.
[PMID: 29423015]
Yu A, Wang Y, Bian Y. et al. IL-1β promotes the nuclear translocaiton of S100A4 protein in gastric cancer cells MGC803 and the cell’s stem-like properties through PI3K pathway. J Cell Biochem 2018; 119(10): 8163-73.
[ ] [PMID: 29932233]
Manning BD, Toker A. AKT/PKB signaling: Navigating the network. Cell 2017; 169(3): 381-405.
[ ] [PMID: 28431241]
Manning BD, Cantley LC. AKT/PKB signaling: Navigating downstream. Cell 2007; 129(7): 1261-74.
[ ] [PMID: 17604717]
Zheng W, Wu C, Wu X, Cai Y, Liu B, Wang C. Genetic variants of autophagy-related genes in the PI3K/Akt/mTOR pathway and risk of gastric cancer in the Chinese population. Gene 2021; 769: 145190.
[ ] [PMID: 33053421]
Zhang Y, Chen L, Cao Y. et al. LETM1 promotes gastric cancer cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. J Gastric Cancer 2020; 20(2): 139-51.
[ ] [PMID: 32595998]
Zhang C, Lin X, Zhao Q. et al. YARS as an oncogenic protein that promotes gastric cancer progression through activating PI3K-Akt signaling. J Cancer Res Clin Oncol 2020; 146(2): 329-42.
[ ] [PMID: 31912229]
Wang RY, Chen XW, Zhang WW, Jiang F, Liu MQ, Shen XB. CYP2E1 changes the biological function of gastric cancer cells via the PI3K/Akt/mTOR signaling pathway. Mol Med Rep 2020; 21(2): 842-50.
[PMID: 31974627]
Qiu L, Ma Z, Li X. et al. DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 path-way. Acta Biochim Biophys Sin (Shanghai) 2020; 52(11): 1202-14.
[ ] [PMID: 33079995]
Wang X, Gao S, Xie F. et al. High expression of TCF12 contributes to gastric cancer development via being target regulated by miR-183 and activating PI3K/AKT pathway. J Cell Biochem 2019; 120(8): 13903-11.
[ ] [PMID: 30982999]
Wang N, Dong Q, Zhou XN. LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling. Am J Transl Res 2019; 11(10): 6534-43.
[PMID: 31737204]
Wang L, Wen X, Luan F. et al. EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway. Cancer Manag Res 2019; 11: 7877-91.
[ ] [PMID: 31686906]
Lu R, Zhao G, Yang Y, Jiang Z, Cai J, Hu H. Inhibition of CD133 overcomes cisplatin resistance through inhibiting PI3K/AKT/mTOR signaling pathway and autophagy in CD133-Positive Gastric Cancer Cells. Technol Cancer Res Treat 2019; 18: 1533033819864311.
[ ] [PMID: 31405336]
Huang YK, Kang WM, Ma ZQ, Liu YQ, Zhou L, Yu JC. NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway. Carcinogenesis 2019; 40(2): 370-9.
[ ] [PMID: 30371738]
Tian L, Zhao Z, Xie L, Zhu J. MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. Oncotarget 2017; 9(4): 4886-96.
[ ] [PMID: 29435149]
Milligan MJ, Lipovich L. Pseudogene-derived lncRNAs: Emerging regulators of gene expression. Front Genet 2015; 5(476): 476.
[ ] [PMID: 25699073]
Huang Y, Zhang J, Hou L. et al. LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway. J Exp Clin Cancer Res 2017; 36(1): 194.
[ ] [PMID: 29282102]
Yan J, Dang Y, Liu S, Zhang Y, Zhang G. LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumour Biol 2016; 37(12): 16345-55.
[ ] [PMID: 27900563]
Li X, Yan X, Wang F. et al. Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer. J Cell Mol Med 2019; 23(4): 2920-32.
[ ] [PMID: 30793479]
Ma F, An K, Li Y. Silencing of long non-coding RNA-HCG18 inhibits the tumorigenesis of gastric cancer through blocking pi3k/akt pathway. OncoTargets Ther 2020; 13: 2225-34.
[ ] [PMID: 32256081]
Liu HT, Ma RR, Lv BB. et al. LncRNA-HNF1A-AS1 functions as a competing endogenous RNA to activate PI3K/AKT signalling pathway by sponging miR-30b-3p in gastric cancer. Br J Cancer 2020; 122(12): 1825-36.
[ ] [PMID: 32336754]
Dai Q, Zhang T, Pan J, Li C. LncRNA UCA1 promotes cisplatin resistance in gastric cancer via recruiting EZH2 and activating PI3K/AKT pathway. J Cancer 2020; 11(13): 3882-92.
[ ] [PMID: 32328192]
Dai Q, Zhang T, Li C. LncRNA MALAT1 regulates the cell proliferation and cisplatin resistance in gastric cancer via PI3K/AKT pathway. Cancer Manag Res 2020; 12: 1929-39.
[ ] [PMID: 32214850]
Zhu K, Ren Q, Zhao Y. lncRNA MALAT1 overexpression promotes proliferation, migration and invasion of gastric cancer by activating the PI3K/AKT pathway. Oncol Lett 2019; 17(6): 5335-42.
[ ] [PMID: 31186750]
Xun J, Wang C, Yao J, Gao B, Zhang L. Long Non-Coding RNA. Long non-coding RNA hotair modulates KLF12 to regulate gastric cancer progression via PI3K/ATK signaling pathway by sponging miR-618. OncoTargets Ther 2019; 12: 10323-34.
[ ] [PMID: 31819516]
Wang LL, Zhang L, Cui XF. Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer. Ther Adv Med Oncol 2019; 11: 1758835919874651.
[ ] [PMID: 31579114]
Li JF, Li WH, Xue LL, Zhang Y. Long non-coding RNA PICART1 inhibits cell proliferation by regulating the PI3K/AKT and MAPK/ERK signaling pathways in gastric cancer. Eur Rev Med Pharmacol Sci 2019; 23(2): 588-97.
[PMID: 30720166]
Liang S, Wei X, Zhang M, Sun C. Preparation of structured lipid enriched with medium chain triacylglycerol by chemical catalyzed acidolysis of coconut oil: Optimized by response surface methodology. J Oleo Sci 2019; 68(12): 1175-85.
[ ] [PMID: 31787671]
Vaughan A, Stevanovic S, Banks APW. et al. The cytotoxic, inflammatory and oxidative potential of coconut oil-substituted diesel emissions on bronchial epithelial cells at an air-liquid interface. Environ Sci Pollut Res Int 2019; 26(27): 27783-91.
[ ] [PMID: 31342346]
Chen P, Zhao X, Wang H, Zheng M, Wang Q, Chang W. The Down-Regulation of lncRNA PCAT18 promotes the progression of gastric cancer via MiR-107/PTEN/PI3K/AKT signaling pathway. OncoTargets Ther 2019; 12: 11017-31.
[ ] [PMID: 31853187]
Cen D, Huang H, Yang L, Guo K, Zhang J. Long noncoding RNA STXBP5-AS1 inhibits cell proliferation, migration, and invasion through inhibiting the PI3K/AKT signaling pathway in gastric cancer cells. OncoTargets Ther 2019; 12: 1929-36.
[ ] [PMID: 30881044]
Yan R, Li K, Yuan DW. et al. Downregulation of microRNA-4295 enhances cisplatin-induced gastric cancer cell apoptosis through the EGFR/PI3K/Akt signaling pathway by targeting LRIG1. Int J Oncol 2018; 53(6): 2566-78.
[ ] [PMID: 30320337]
Zhang H, Li L, Yuan C, Wang C, Gao T, Zheng Z. MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway. World J Surg Oncol 2020; 18(1): 73.
[ ] [PMID: 32284070]
Streleckiene G, Inciuraite R, Juzenas S. et al. miR-20b and miR-451a are involved in gastric carcinogenesis through the PI3K/AKT/mTOR signaling pathway: Data from gastric cancer patients, cell lines and Ins-Gas mouse model. Int J Mol Sci 2020; 21(3): E877.
[ ] [PMID: 32013265]
Ni QF, Zhang Y, Yu JW, Hua RH, Wang QH, Zhu JW. miR-92b promotes gastric cancer growth by activating the DAB2IPmediated PI3K/AKT signalling pathway. Cell Prolif 2020; 53(1): e12630.
[ ] [PMID: 31713929]
Li J, Ye D, Shen P. et al. Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway. J Exp Clin Cancer Res 2020; 39(1): 212.
[ ] [PMID: 33032635]
Hu ZH, Wang GJ, Li RX. et al. Upregulation of miR-133a-3p enhances Bufothionine-induced gastric cancer cell death by modulating IGF1R/PI3K/Akt signal pathway mediated ER stress. Life Sci 2020; 259: 118180.
[ ] [PMID: 32758622]
Gu Y, Fei Z, Zhu R. miR-21 modulates cisplatin resistance of gastric cancer cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Anticancer Drugs 2020; 31(4): 385-93.
[ ] [PMID: 31913198]
Wang Q, He Y, Kan W. et al. microRNA-32-5p targets KLF2 to promote gastric cancer by activating PI3K/AKT signaling pathway. Am J Transl Res 2019; 11(8): 4895-908.
[PMID: 31497207]
Wang L, Li K, Wang C, Shi X, Yang H. miR-107 regulates growth and metastasis of gastric cancer cells via activation of the PI3KAKT signaling pathway by down-regulating FAT4. Cancer Med 2019; 8(11): 5264-73.
[ ] [PMID: 31297980]
Li H, He C, Wang X, Wang H, Nan G, Fang L. MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals. Artif Cells Nanomed Biotechnol 2019; 47(1): 3163-71.
[ ] [PMID: 31352788]
Jiang K, Xie LF, Xiao TZ, Qiu MY, Wang WL. MiR-181d inhibits cell proliferation and metastasis through PI3K/AKT pathway in gastric cancer. Eur Rev Med Pharmacol Sci 2019; 23(20): 8861-9.
[PMID: 31696473]
Zhang F, Li K, Pan M. et al. miR-589 promotes gastric cancer aggressiveness by a LIFR-PI3K/AKT-c-Jun regulatory feedback loop. J Exp Clin Cancer Res. CR (East Lansing Mich) 2018; 37(1): 152.
Duan H, Qu L, Shou C. Activation of EGFR-PI3K-AKT signaling is required for Mycoplasma hyorhinis-promoted gastric cancer cell migration. Cancer Cell Int 2014; 14(1): 135.
[ ] [PMID: 25505372]
Zhu Y, Kong F, Zhang C. et al. CD133 mediates the TGF-β1-induced activation of the PI3K/ERK/P70S6K signaling pathway in gastric cancer cells. Oncol Lett 2017; 14(6): 7211-6.
[ ] [PMID: 29344155]
Zhang J, Xu J, Dong Y, Huang B. Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression. Biosci Rep 2018; 38(6): BSR20180741.
[ ] [PMID: 29899167]
Redlak MJ, Miller TA. Targeting PI3K/Akt/HSP90 signaling sensitizes gastric cancer cells to deoxycholate-induced apoptosis. Dig Dis Sci 2011; 56(2): 323-9.
[ ] [PMID: 20585984]
Cao Y, Qu J, Li C. et al. Celecoxib sensitizes gastric cancer to rapamycin via inhibition of the Cbl-b-regulated PI3K/Akt pathway. Tumour Biol 2015; 36(7): 5607-15.
[ ] [PMID: 25701378]
Liu M, Li CM, Chen ZF. et al. Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells. Int J Mol Med 2014; 33(6): 1451-8.
[ ] [PMID: 24676394]
Zhang CΗ, Awasthi N, Schwarz MA, Schwarz RE. The dual PI3K/mTOR inhibitor NVP-BEZ235 enhances nab-paclitaxel antitumor response in experimental gastric cancer. Int J Oncol 2013; 43(5): 1627-35.
[ ] [PMID: 24042258]
Yang L, Yang G, Ding Y. et al. Combined treatment with PI3K inhibitor BKM120 and PARP inhibitor olaparib is effective in inhibiting the gastric cancer cells with ARID1A deficiency. Oncol Rep 2018; 40(1): 479-87.
[ ] [PMID: 29767248]
Jia X, Wen Z, Sun Q. et al. Apatinib suppresses the proliferation and apoptosis of gastric cancer cells via the PI3K/Akt signaling pathway. J BUON 2019; 24(5): 1985-91.
Xu C, Gu K, Yasen Y, Hou Y. Efficacy and safety of celecoxib therapy in osteoarthritis: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016; 95(20): e3585-5.
[ ] [PMID: 27196460]
Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: A systematic review and meta-analysis. J R Soc Med 2006; 99(3): 132-40.
[ ] [PMID: 16508052]
Liu G, Wang C, He Y. e M. Application effect of apatinib in patients with failure of standard treatment for advanced malignant tumours. BMC Pharmacol Toxicol 2019; 20(1): 61.
[ ] [PMID: 31661009]
Yang Y, Wu X, Li F. et al. Evaluation of efficacy and safety of apatinib treatment in advanced gastric cancer. J Cancer Res Ther 2019; 15(2): 365-9.
[PMID: 30964112]
Ando Y, Inada-Inoue M, Mitsuma A. et al. Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci 2014; 105(3): 347-53.
[ ] [PMID: 24405565]
Rodon J, Braña I, Siu LL. et al. Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Invest New Drugs 2014; 32(4): 670-81.
[ ] [PMID: 24652201]
Netland IA, Førde HE, Sleire L. et al. Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models. BMC cancer 2016; 16(657): 016-2712.
Zhang N, Xing X, Gu F, Zhou G, Liu X, Li B. Ropivacaine Inhibits the Growth, Migration and Invasion of Gastric Cancer Through Attenuation of WEE1 and PI3K/AKT Signaling via miR-520a-3p. OncoTargets Ther 2020; 13: 5309-21.
[ ] [PMID: 32606749]
Lv GB, Wang TT, Zhu HL, Wang HK, Sun W, Zhao LF. Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway. FEBS Open Bio 2020; 10(10): 2157-65.
[ ] [PMID: 32750222]
Kim KJ, Kim JW, Sung JH. et al. PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer. Sci Rep 2020; 10(1): 12308.
[ ] [PMID: 32704014]
Dai J, Liu D, Chen L, Sun L. Effect of Ag-1031 on apoptosis in gastric cancer AGS cells and its effects on the PI3K/AKT/mTOR signaling pathway. Biotechnol Lett 2020; 42(11): 2447-52.
[ ] [PMID: 32651704]
Liu JZ, Hu YL, Feng Y. et al. Rafoxanide promotes apoptosis and autophagy of gastric cancer cells by suppressing PI3K /Akt/mTOR pathway. Exp Cell Res 2019; 385(2): 111691.
[ ] [PMID: 31678170]
Kim MY, Kruger AJ, Jeong JY. et al. Combination therapy with a PI3K/mTOR dual inhibitor and chloroquine enhances synergistic apoptotic cell death in epstein-barr virus-infected gastric cancer cells. Mol Cells 2019; 42(6): 448-59.
[ ] [PMID: 31085812]
Wang Y, Cui P, Liu J, Wu H, Ma J. Aclidinium bromide inhibits the growth and metastasis of gastric cancer MKN 28 cells via the PI3K signaling pathway. Mol Med Rep 2018; 18(2): 2263-8.
[ ] [PMID: 29956761]
Li L, Zhang S, Xie D, Chen H, Zheng X, Pan D. Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy. OncoTargets Ther 2018; 11: 6111-8.
[ ] [PMID: 30275715]
Chen D, Lin X, Zhang C. et al. Dual PI3K/mTOR inhibitor BEZ235 as a promising therapeutic strategy against paclitaxelresistant gastric cancer via targeting PI3K/Akt/mTOR pathway. Cell Death Dis 2018; 9(2): 123.
[ ] [PMID: 29374144]
Zhu Y, Tian T, Zou J. et al. Dual PI3K/mTOR inhibitor BEZ235 exerts extensive antitumor activity in HER2-positive gastric cancer. BMC Cancer 2015; 15(1): 894.
[ ] [PMID: 26560145]
Xia LJ, Wu YL, Zhang FC. Combination of cecropinXJ and LY294002 induces synergistic cytotoxicity, and apoptosis in human gastric cancer cells via inhibition of the PI3K/Akt signaling pathway. Oncol Lett 2017; 14(6): 7522-8.
[ ] [PMID: 29344198]
Yuan CX, Zhou ZW, Yang YX. et al. Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells. Drug Des Devel Ther 2015; 9: 1293-318.
[PMID: 25767376]
Mao Z, Zhou J, Luan J, Sheng W, Shen X, Dong X. Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells. Biomed Pharmacothe 2014; 68(2): 179-83.
Palvai S, Kuman MM, Sengupta P, Basu S. Hyaluronic acid layered chimeric nanoparticles: Targeting MAPK-PI3K signaling hub in colon cancer cells. ACS Omega 2017; 2(11): 7868-80.
[ ] [PMID: 30023564]
Chen Y, Lee CH, Tseng BY. et al. AZD8055 exerts antitumor effects on colon cancer cells by inhibiting mTOR and cell-cycle progression. Anticancer Res 2018; 38(3): 1445-54.
[PMID: 29491070]
Arisan ED, Ergül Z, Bozdağ G. et al. Diclofenac induced apoptosis via altering PI3K/Akt/MAPK signaling axis in HCT 116 more efficiently compared to SW480 colon cancer cells. Mol Biol Rep 2018; 45(6): 2175-84.
[ ] [PMID: 30406888]
Shen Q, Zhang L, Liao Z. et al. The genome of artemisia annua provides insight into the evolution of asteraceae family and artemisinin biosynthesis. Mol Plant 2018; 11(6): 776-88.
[ ] [PMID: 29703587]
Roper J, Richardson MP, Wang WV. et al. The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer. PLoS One 2011; 6(9): e25132.
[ ] [PMID: 21966435]
Alqurashi N, Hashimi SM, Alowaidi F, Ivanovski S, Wei MQ. Dual mTOR/PI3K inhibitor NVP BEZ235 arrests colorectal cancer cell growth and displays differential inhibition of 4E BP1. Oncol Rep 2018; 40(2): 1083-92.
[ ] [PMID: 29845289]
Kim JS, Kim JE, Kim K. et al. The impact of cetuximab plus AKT or mTOR- inhibitor in a patient-derived colon cancer cell model with wild-type RAS and PIK3CA mutation. J Cancer 2017; 8(14): 2713-9.
[ ] [PMID: 28928860]
Nagappan A, Lee WS, Yun JW. et al. Tetraarsenic hexoxide induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells. PLoS One 2017; 12(3): e0174591.
[ ] [PMID: 28355296]
Liu L, Gao H, Wang H. et al. Catalpol promotes cellular apoptosis in human HCT116 colorectal cancer cells via microRNA-200 and the downregulation of PI3K-Akt signaling pathway. Oncol Lett 2017; 14(3): 3741-7.
[ ] [PMID: 28927141]
Amerizadeh F, Rezaei N, Rahmani F. et al. Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem 2018; 119(12): 10250-61.
[ ] [PMID: 30129057]
Fu Z, Han X, Du J. et al. Euphorbia lunulata extract acts on multidrug resistant gastric cancer cells to inhibit cell proliferation, migration and invasion, arrest cell cycle progression, and induce apoptosis. J Ethnopharmacol 2018; 212: 8-17.
[ ] [PMID: 28811220]
Qian Y, Yan Y, Lu H. et al. Celastrus orbiculatus extracts inhibit the metastasis through attenuating PI3K/Akt/mTOR signaling pathway in human gastric cancer. Anticancer Agents Med Chem 2019; 19(14): 1754-61.
[ ] [PMID: 31364518]
Lee HJ, Venkatarame Gowda Saralamma V, Kim SM. et al. Pectolinarigenin induced cell cycle arrest, autophagy, and apoptosis in gastric cancer cell via PI3K/AKT/mTOR signaling pathway. Nutrients 2018; 10(8): E1043.
[ ] [PMID: 30096805]
Guo D, Zhang B, Liu S, Jin M. Xanthohumol induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI3K/Akt/mTOR-kinase in human gastric cancer cells. Biomed Pharmacothe 2018; 106: 1300-6.
Fu H, Wang C, Yang D. et al. Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J Cell Physiol 2018; 233(6): 4634-42.
[ ] [PMID: 28926094]
Lu X, Li Y, Li X, Aisa HA. Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer. Oncol Lett 2017; 14(2): 1993-2000.
[ ] [PMID: 28789432]
Hao W, Yuan X, Yu L. et al. Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways. Sci Rep 2015; 5(1): 10336.
[ ] [PMID: 25981581]
Liu Q, Dong HW, Sun WG. et al. Apoptosis initiation of β-ionone in SGC-7901 gastric carcinoma cancer cells via a PI3K-AKT pathway. Arch Toxicol 2013; 87(3): 481-90.
[ ] [PMID: 23100158]
Kwon MJ, Nam TJ. A polysaccharide of the marine alga Capsosiphon fulvescens induces apoptosis in AGS gastric cancer cells via an IGF-IR-mediated PI3K/Akt pathway. Cell Biol Int 2007; 31(8): 768-75.
[ ] [PMID: 17344071]
Li D, Qu X, Hou K. et al. PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs 2009; 20(1): 59-64.
[ ] [PMID: 19343001]
Zhao JG, Zhang L, Xiang XJ. et al. Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway. J BUON 2016; 21(3): 609-17.
Illam SP, Narayanankutty A, Mathew SE, Valsalakumari R, Jacob RM, Raghavamenon AC. Epithelial mesenchymal transition in cancer progression: Prev entive phytochemicals. Recent Patents Anticancer Drug Discov 2017; 12(3): 234-46.
[ ] [PMID: 28440207]
Feng LM, Wang XF, Huang QX. Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway. J Biosci 2017; 42(4): 547-54.
[ ] [PMID: 29229873]
Zhu J, Wen K. Astragaloside IV inhibits TGF-β1-induced epithelial-mesenchymal transition through inhibition of the PI3K/Akt/NF-κB pathway in gastric cancer cells. Phytother Res 2018; 32(7): 1289-96.
[ ] [PMID: 29480652]
Ho HH, Chang CS, Ho WC, Liao SY, Wu CH, Wang CJ. Antimetastasis effects of gallic acid on gastric cancer cells involves inhibition of NF-kappaB activity and downregulation of PI3K/AKT/small GTPase signals. Food and chemical toxicology : An international journal published for the British Industrial Biological Research Association 2010; 48(8-9): 2508-16.
Ma NX, Sun W, Wu J. et al. Compound wumei powder inhibits the invasion and metastasis of gastric cancer via Cox-2/PGE2-PI3K/AKT/GSK3β/β-catenin signaling pathway. Evid Based Complement Alternat Med 2017; 2017: 3039450.
[ ] [PMID: 29358963]
Zhang XR, Wang SY, Sun W, Wei C. Isoliquiritigenin inhibits proliferation and metastasis of MKN28 gastric cancer cells by suppressing the PI3K/AKT/mTOR signaling pathway. Mol Med Rep 2018; 18(3): 3429-36.
[ ] [PMID: 30066879]
Wang D, Xin Y, Tian Y, Li W, Sun D, Yang Y. Pseudolaric acid B inhibits gastric cancer cell metastasis in vitro and in haematogenous dissemination model through PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways. Exp Cell Res 2017; 352(1): 34-44.
[ ] [PMID: 28132880]
Shen X, Si Y, Wang Z, Wang J, Guo Y, Zhang X. Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling. Int J Mol Med 2016; 38(2): 619-26.
[ ] [PMID: 27278820]
Luo Y, Zha L, Luo L. et al. [6]-Gingerol enhances the cisplatin sensitivity of gastric cancer cells through inhibition of proliferation and invasion via PI3K/AKT signaling pathway. Phytother Res 2019; 33(5): 1353-62.
[ ] [PMID: 30811726]
Kim SM, Vetrivel P, Ha SE, Kim HH, Kim JA, Kim GS. Apigetrin induces extrinsic apoptosis, autophagy and G2/M phase cell cycle arrest through PI3K/AKT/mTOR pathway in AGS human gastric cancer cell. J Nutr Biochem 2020; 83: 108427.
[ ] [PMID: 32559585]
Lin F, Yang J, Muhammad U. et al. Bacillomycin D-C16 triggers apoptosis of gastric cancer cells through the PI3K/Akt and FoxO3a signaling pathways. Anticancer Drugs 2019; 30(1): 46-55.
[ ] [PMID: 30169424]
Song M, Wang X, Luo Y. et al. Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1. Chem Biol Interact 2020; 317: 108939.
[ ] [PMID: 31945315]
Huang X, Qian J, Li L. et al. Curcumol improves cisplatin sensitivity of human gastric cancer cells through inhibiting PI3K/AKT pathway. Drug Dev Res 2020; 81(8): 1019-25.
[ ] [PMID: 32715509]
Deen A, Visvanathan R, Wickramarachchi D. et al. Chemical composition and health benefits of coconut oil: an overview. J Sci Food Agric 2020.
[PMID: 33022082]
Zheng Y, Guo C, Zhang X, Wang X, Ma A. Garcinol acts as an antineoplastic agent in human gastric cancer by inhibiting the PI3K/AKT signaling pathway. Oncol Lett 2020; 20(1): 667-76.
[ ] [PMID: 32565991]
Peng X, Ruan C, Lei C. et al. Anticancer effects of Lanostane against human gastric cancer cells involves autophagy, apoptosis and modulation of m-TOR/PI3K/AKT signalling pathway. J BUON 2020; 25(3): 1463-8.
Yang JH, Yu K, Si XK. et al. Liensinine inhibited gastric cancer cell growth through ROS generation and the PI3K/AKT pathway. J Cancer 2019; 10(25): 6431-8.
[ ] [PMID: 31772676]
Liang L, Amin A, Cheung WY. et al. Parameritannin A-2 from Urceola huaitingii enhances doxorubicin-induced mitochondriadependent apoptosis by inhibiting the PI3K/Akt, ERK1/2 and p38 pathways in gastric cancer cells. Chem Biol Interact 2020; 316: 108924.
[ ] [PMID: 31843629]
Rong L, Li Z, Leng X. et al. Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway. Biomed Pharmacother 2020; 122: 109726.
Liu Y, Liu C, Tan T, Li S, Tang S, Chen X. Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway. Anticancer Drugs 2019; 30(10): 983-90.
[ ] [PMID: 31609766]
Wu YJ, Lin SH, Din ZH, Su JH, Liu CI. Sinulariolide Inhibits Gastric Cancer Cell Migration and Invasion through downregulation of the EMT Process and Suppression of FAK/PI3K/AKT/mTOR and MAPKs signaling pathways. Mar Drugs 2019; 17(12): E668.
[ ] [PMID: 31783709]
Zhang K, Liu W, Qu Z. et al. In vitro and in vivo human gastric cancer inhibition by Trifolirhizin is facilitated via autophagy, mitochondrial mediated programmed cell death, G2/M phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway. J BUON: 2019; 24(3): 1100-5.
Yu J, Song S, Jiao J. et al. Zi Yin Hua Tan recipe inhibits cell proliferation and promotes apoptosis in gastric cancer by suppressing PI3K/AKT pathway. BioMed Res Int 2020; 2020: 2018162.
[ ] [PMID: 32382534]
Liu YQ, Wang SK, Xu QQ. et al. Acetyl-11-keto-beta-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties. Acta Pharmacol Sin 2018; 31(10): 018-0157.
Li W, Liu J, Fu W. et al. 3-O-acetyl-11-keto-β-boswellic acid exerts anti-tumor effects in glioblastoma by arresting cell cycle at G2/M phase. J Exp Clin Cancer Res 2018; 37(1): 132.
[ ] [PMID: 29970196]
Amin A, Farrukh A, Murali C. et al. Saffron and its major ingredients’ effect on colon cancer cells with mismatch repair deficiency and microsatellite instability. Molecules 2021; 26(13): 3855.
[ ] [PMID: 34202689]
Wang D, Ge S, Bai J, Song Y. Boswellic acid exerts potent anticancer effects in HCT-116 human colon cancer cells mediated via induction of apoptosis, cell cycle arrest, cell migration inhibition and inhibition of PI3K/AKT signalling pathway. J BUON 2018; 23(2): 340-5.
Tsai DH, Chung CH, Lee KT. Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells. Sci Rep 2018; 8(1): 17424.
[ ] [PMID: 30479369]
Han C, Xing G, Zhang M. et al. Wogonoside inhibits cell growth and induces mitochondrial-mediated autophagy-related apoptosis in hu-man colon cancer cells through the PI3K/AKT/mTOR/p70S6K signaling pathway. Oncol Lett 2018; 15(4): 4463-70.
[ ] [PMID: 29541215]
Sun Y, Zhao Y, Wang X. et al. Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway. Oncotarget 2016; 7(23): 34300-15.
[ ] [PMID: 27102438]
Li Q, Lai Z, Yan Z. et al. Hedyotis diffusa Willd inhibits proliferation and induces apoptosis of 5 FU resistant colorectal cancer cells by regulating the PI3K/AKT signaling pathway. Mol Med Rep 2018; 17(1): 358-65.
[PMID: 29115462]
Hu T, Li Z, Gao C-Y, Cho CH. Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World J Gastroenterol 2016; 22(30): 6876-89.
[ ] [PMID: 27570424]
Eduati F, Doldàn-Martelli V, Klinger B. et al. Drug resistance mechanisms in colorectal cancer dissected with cell type-specific dynamic logic models. Cancer Res 2017; 77(12): 3364-75.
[ ] [PMID: 28381545]
Bufu T, Di X, Yilin Z, Gege L, Xi C, Ling W. Celastrol inhibits colorectal cancer cell proliferation and migration through suppression of MMP3 and MMP7 by the PI3K/AKT signaling pathway. Anticancer Drugs 2018; 29(6): 530-8.
[ ] [PMID: 29553945]
Sun D, Zhang F, Qian J. et al. 4′-hydroxywogonin inhibits colorectal cancer angiogenesis by disrupting PI3K/AKT signaling. Chem Biol Interact 2018; 296: 26-33.
[ ] [PMID: 30217479]
Mi C, Ma J, Wang KS. et al. Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1α via the mTOR/p70S6K/4E-BP1 and MAPK pathways. J Ethnopharmacol 2017; 203: 27-38.
[ ] [PMID: 28341244]
Liu M, Zhao G, Zhang D. et al. Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells. Int J Oncol 2018; 53(3): 1363-73.
[ ] [PMID: 30015913]
Kumar S, Agnihotri N. Piperlongumine, a piper alkaloid targets Ras/PI3K/Akt/mTOR signaling axis to inhibit tumor cell growth and proliferation in DMH/DSS induced experimental colon cancer. Biomed Pharmacother 2019; 109: 1462-77.
Zhang L, Chen C, Duanmu J. et al. Cryptotanshinone inhibits the growth and invasion of colon cancer by suppressing inflammation and tumor angiogenesis through modulating MMP/TIMP system, PI3K/Akt/mTOR signaling and HIF-1α nuclear translocation. Int Immunopharmacol 2018; 65: 429-37.
[ ] [PMID: 30388517]
Zeng YH, Zhou LY, Chen QZ. et al. Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells. Oncol Rep 2017; 38(1): 456-64.
[ ] [PMID: 28534975]
Liu YZ, Wu K, Huang J. et al. The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int J Oncol 2014; 45(1): 104-12.
[ ] [PMID: 24756222]
Han B, Jiang P, Li Z. et al. Coptisine-induced apoptosis in human colon cancer cells (HCT-116) is mediated by PI3K/Akt and mitochondrial-associated apoptotic pathway. Phytomedicine: international journal of phytotherapy and phytopharmacology 2018; 48: 152-60.
Daaboul HE, Daher CF, Bodman-Smith K. et al. Antitumor activity of β-2-himachalen-6-ol in colon cancer is mediated through its inhibition of the PI3K and MAPK pathways. Chem Biol Interact 2017; 275: 162-70.
[ ] [PMID: 28782499]
Attia YM, El-Kersh DM, Wagdy HA, Elmazar MM. Verbascoside: Identification, quantification, and potential sensitization of colorectal cancer cells to 5-FU by targeting PI3K/AKT pathway. Sci Rep 2018; 8(1): 16939.
[ ] [PMID: 30446678]
Soo HC, Chung FF, Lim KH. et al. Cudraflavone C induces tumorspecific apoptosis in colorectal cancer cells through inhibition of the phosphoinositide 3-Kinase (PI3K)-AKT pathway. PLoS One 2017; 12(1): e0170551.
[ ] [PMID: 28107519]
Lin J, Feng J, Yang H. et al. Scutellaria barbata D. Don inhibits 5-fluorouracil resistance in colorectal cancer by regulating PI3K/AKT pathway. Oncol Rep 2017; 38(4): 2293-300.
[ ] [PMID: 28849113]
Jin Y, Chen W, Yang H. et al. Scutellaria barbata D. Don inhibits migration and invasion of colorectal cancer cells via suppression of PI3K/AKT and TGF-β/Smad signaling pathways. Exp Ther Med 2017; 14(6): 5527-34.
[ ] [PMID: 29285087]
Zhang J, Jiang H, Xie L. et al. Antitumor effect of manumycin on colorectal cancer cells by increasing the reactive oxygen species produc-tion and blocking PI3K-AKT pathway. OncoTargets Ther 2016; 9: 2885-95.
[ ] [PMID: 27307747]
Wani ZA, Guru SK, Rao AV. et al. A novel quinazolinone chalcone derivative induces mitochondrial dependent apoptosis and inhibits PI3K/Akt/mTOR signaling pathway in human colon cancer HCT-116 cells. Food Chem Toxicol: an international journal published for the British Industrial Biological Research Association 2016; 87: 1-11.
Arun A, Patel OPS, Saini D, Yadav PP, Konwar R. Anti-colon cancer activity of Murraya koenigii leaves is due to constituent murrayazoline and O-methylmurrayamine A induced mTOR/AKT downregulation and mitochondrial apoptosis. Biomed Pharmacother 2017; 93: 510-21.
Zhao X, Li X, Ren Q, Tian J, Chen J. Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways. Gene 2016; 591(1): 123-8.
[ ] [PMID: 27393650]
Cadoná FC, Rosa JL, Schneider T. et al. Guaraná, a highly caffeinated food, presents in vitro antitumor activity in colorectal and breast cancer cell lines by inhibiting AKT/mTOR/S6K and MAPKs pathways. Nutr Cancer 2017; 69(5): 800-10.
[ ] [PMID: 28569556]
Yang L, Liu Y, Wang M. et al. Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells. Oncol Lett 2016; 12(5): 3771-8.
[ ] [PMID: 27895729]
Li N, Zhang Z, Jiang G, Sun H, Yu D. Nobiletin sensitizes colorectal cancer cells to oxaliplatin by PI3K/Akt/MTOR pathway. Front Biosci 2019; 24(2): 303-12.
[ ] [PMID: 30468657]
Yan H, Jung KH, Kim J, Rumman M, Oh MS, Hong SS. Artemisia capillaris extract AC68 induces apoptosis of hepatocellular carcinoma by blocking the PI3K/AKT pathway. Biomed Pharmacother 2018; 98: 134-41.
Lim EG, Kim GT, Kim BM, Kim EJ, Kim SY, Kim YM. Ethanol extract from Cnidium monnieri (L.) Cusson induces cell cycle arrest and apoptosis via regulation of the p53 independent pathway in HepG2 and Hep3B hepatocellular carcinoma cells. Mol Med Rep 2018; 17(2): 2572-80.
[PMID: 29207130]
Kim BR, Ha J, Lee S, Park J, Cho S. Anti-cancer effects of ethanol extract of Reynoutria japonica Houtt. radix in human hepatocellular carcinoma cells via inhibition of MAPK and PI3K/Akt signaling pathways. J Ethnopharmacol 2019; 245: 112179.
[ ] [PMID: 31445130]
Zhou LJ, Mo YB, Bu X. et al. Erinacine facilitates the opening of the mitochondrial permeability transition pore through the inhibition of the PI3K/ Akt/GSK-3beta signaling pathway in human hepatocellular carcinoma. Cell Physiol Biochem 2018; 50(3): 851-67.
Ahn H, Im E, Lee DY, Lee HJ, Jung JH, Kim SH. Antitumor effect of pyrogallol via miR-134 mediated S phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling in hepatocellular carcinoma. Int J Mol Sci 2019; 20(16): E3985.
[ ] [PMID: 31426282]
Hamza AA, Heeba GH, Hamza S, Abdalla A, Amin A. Standardized extract of ginger ameliorates liver cancer by reducing proliferation and inducing apoptosis through inhibition oxidative stress/ inflammation pathway. Biomed Pharmacother 2021; 134(111102): 15.
Yang J, Pi C, Wang G. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother 2018; 103: 699-707.
Hua H, Zhu Y, Song YH. Ruscogenin suppressed the hepatocellular carcinoma metastasis via PI3K/Akt/mTOR signaling pathway. Biomed Pharmacother 2018; 101: 115-22.
Xing S, Yu W, Zhang X. et al. Isoviolanthin extracted from dendrobium officinale reverses tgf-β1-mediated epithelialmesenchymal transition in hepatocellular carcinoma cells via deactivating the tgf-β/smad and pi3k/akt/mtor signaling pathways. Int J Mol Sci 2018; 19(6): E1556.
[ ] [PMID: 29882900]
Ye R, Dai N, He Q. et al. Comprehensive anti-tumor effect of Brusatol through inhibition of cell viability and promotion of apoptosis caused by autophagy via the PI3K/Akt/mTOR pathway in hepatocellular carcinoma. Biomed Pharmacother 2018; 105: 962-73.
Liao ZH, Zhu HQ, Chen YY. et al. The epigallocatechin gallate derivative Y6 inhibits human hepatocellular carcinoma by inhibiting angio-genesis in MAPK/ERK1/2 and PI3K/AKT/ HIF-1α/VEGF dependent pathways. J Ethnopharmacol 2020; 259: 112852.
[ ] [PMID: 32278759]
Murali C, Mudgil P, Gan CY. et al. Camel whey protein hydrolysates induced G2/M cellcycle arrest in human colorectal carcinoma. Sci Rep 2021; 11(1): 021-86391
Juaid N, Amin A, Abdalla A. et al. Anti-hepatocellular carcinoma biomolecules: molecular targets insights. Int J Mol Sci 2021; 22(19): 10774.
[ ] [PMID: 34639131]
El-Dakhly SM, Salama AAA, Hassanin SOM, Yassen NN, Hamza AA, Amin A. Aescin and diosmin each alone or in low dose- combination ameliorate liver damage induced by carbon tetrachloride in rats. BMC Research Notes 2020; 13(1): 020-05094
Gao AM, Ke ZP, Wang JN, Yang JY, Chen SY, Chen H. Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis 2013; 34(8): 1806-14.
[ ] [PMID: 23563091]
Liou A-T, Chen M-F, Yang C-W. Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTENFOXO4 Pathway. Evid Based Complement Alternat Med 2017; 2017: 4063865.
[ ] [PMID: 28769986]
Chang M, Wu M, Li H. Curcumin combined with glycyrrhetinic acid inhibits the development of hepatocellular carcinoma cells by down-regulating the PTEN/PI3K/AKT signalling pathway. Am J Transl Res 2017; 9(12): 5567-75.
[PMID: 29312508]
Chai R, Fu H, Zheng Z, Liu T, Ji S, Li G. Resveratrol inhibits proliferation and migration through SIRT1 mediated post translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Mol Med Rep 2017; 16(6): 8037-44.
[ ] [PMID: 28983625]
Chiablaem K, Lirdprapamongkol K, Keeratichamroen S, Surarit R, Svasti J. Curcumin suppresses vasculogenic mimicry capacity of hepatocellular carcinoma cells through STAT3 and PI3K/AKT inhibition. Anticancer Res 2014; 34(4): 1857-64.
[PMID: 24692720]
Shi Y, Song Q, Hu D, Zhuang X, Yu S, Teng D. Oleanolic acid induced autophagic cell death in hepatocellular carcinoma cells via PI3K/Akt/mTOR and ROS-dependent pathway. Korean J Physiol Pharmacol 2016; 20(3): 237-43.
[ ] [PMID: 27162477]
Maurya AK, Vinayak M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol Biol Rep 2015; 42(9): 1419-29.
[ ] [PMID: 26311153]
Zhao L, Sha YY, Zhao Q. et al. Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway. Biochemistry and cell biology = Biochimie et biologie cellulaire 2013; 91(4): 221-9.
Lin W, Zhong M, Yin H. et al. Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep 2016; 36(2): 961-7.
[ ] [PMID: 27278720]
Hsieh MJ, Yeh CB, Chiou HL, Hsieh MC, Yang SF. Dioscorea nipponica attenuates migration and invasion by inhibition of urokinase-type plasminogen activator through involving pi3k/akt and transcriptional inhibition of nf-[formula: see text]b and sp-1 in hepatocellular carcinoma. Am J Chin Med 2016; 44(1): 177-95.
[ ] [PMID: 26916922]
Wu YJ, Neoh CA, Tsao CY, Su JH, Li HH. Sinulariolide Suppresses Human Hepatocellular Carcinoma Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 through MAPKs and PI3K/Akt Signaling Pathways. Int J Mol Sci 2015; 16(7): 16469-82.
[ ] [PMID: 26204832]
Lin JJ, Su JH, Tsai CC, Chen YJ, Liao MH, Wu YJ. 11-epi-Sinulariolide acetate reduces cell migration and invasion of human hepatocellular carcinoma by reducing the activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR signaling pathways. Mar Drugs 2014; 12(9): 4783-98.
[ ] [PMID: 25222667]
Zhang Y, Li K, Ying Y. et al. C21 steroid-enriched fraction refined from Marsdenia tenacissima inhibits hepatocellular carcinoma through the coordination of Hippo-Yap and PTEN-PI3K/AKT signaling pathways. Oncotarget 2017; 8(66): 110576-91.
[ ] [PMID: 29299170]
Xu W, Huang JJ, Cheung PC. Extract of Pleurotus pulmonarius suppresses liver cancer development and progression through inhibition of VEGF-induced PI3K/AKT signaling pathway. PLoS One 2012; 7(3): e34406.
[ ] [PMID: 22470568]
Hong SW, Jung KH, Lee HS. et al. SB365 inhibits angiogenesis and induces apoptosis of hepatocellular carcinoma through modulation of PI3K/Akt/mTOR signaling pathway. Cancer Sci 2012; 103(11): 1929-37.
[ ] [PMID: 22909393]
Chen J, Jin X, Chen J, Liu C. Glycyrrhiza polysaccharide induces apoptosis and inhibits proliferation of human hepatocellular carcinoma cells by blocking PI3K/AKT signal pathway. Tumour Biol 2013; 34(3): 1381-9.
[ ] [PMID: 23580179]
Baig B, Halim SA, Farrukh A, Greish Y, Amin A. Current status of nanomaterial-based treatment for hepatocellular carcinoma. Biomed Pharmacother 2019; 116(108852): 15.
El-Kharrag R, Amin A, Hisaindee S, Greish Y, Karam SM. Development of a therapeutic model of precancerous liver using crocin-coated magnetite nanoparticles. Int J Oncol 2017; 50(1): 212-22.
[ ] [PMID: 27878253]
Ratan ZA, Haidere MF, Nurunnabi M. et al. Green chemistry synthesis of silver nanoparticles and their potential anticancer effects. Cancers (Basel) 2020; 12(4): 855.
[ ] [PMID: 32244822]
Tsujimoto H, Morimoto Y, Takahata R. et al. Theranostic photosensitive nanoparticles for lymph node metastasis of gastric cancer. Ann Surg Oncol 2015; 22(3): 015-4594
Qian H, Qian K, Cai J, Yang Y, Zhu L, Liu B. Therapy for Gastric cancer with peritoneal metastasis using injectable albumin hydrogel hybridized with paclitaxel-loaded red blood cell membrane nanoparticles. ACS Biomater Sci Eng 2019; 5(2): 1100-12.
[ ] [PMID: 33405800]
Huo J. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells. Artif Cells Nanomed Biotechnol 2016; 44(5): 1232-5.
[ ] [PMID: 25794798]
Mousavi B, Tafvizi F, Zaker Bostanabad S. Green synthesis of silver nanoparticles using Artemisia turcomanica leaf extract and the study of anti-cancer effect and apoptosis induction on gastric cancer cell line (AGS). Artificial cells, nanomedicine, and biotechnology 2018; 46(sup1): 499-510.
Tang Q, Xia H, Liang W, Huo X, Wei X. Synthesis and characterization of zinc oxide nanoparticles from Morus nigra and its anticancer activity of AGS gastric cancer cells. J Photochem Photobiol B 2020; 202: 111698.
[ ] [PMID: 31734436]
Zhang C, Awasthi N, Schwarz MA, Hinz S, Schwarz RE. Superior antitumor activity of nanoparticle albumin-bound paclitaxel in experimental gastric cancer. PLoS One 2013; 8(2): e58037.
[ ] [PMID: 23460921]
Zhang Y, Tan J, Zhou L, Shan X, Liu J, Ma Y. Synthesis and application of as1411-functionalized gold nanoparticles for targeted therapy of gastric cancer. ACS Omega 2020; 5(48): 31227-33.
[ ] [PMID: 33324832]
Lin Y-H, Chen Z-R, Lai C-H, Hsieh C-H, Feng C-L. Active targeted nanoparticles for oral administration of gastric cancer therapy. Biomacromolecules 2015; 16(9): 3021-32.
[ ] [PMID: 26286711]
Hu N, Yin JF, Ji Z. et al. Strengthening Gastric Cancer Therapy by trastuzumab-conjugated nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine. Cell Physiol Biochem 2017; 44(6): 2158-73.
[ ] [PMID: 29241186]
Hashemi SF, Tasharrofi N, Saber MM. Green synthesis of silver nanoparticles using Teucrium polium leaf extract and assessment of their antitumor effects against MNK45 human gastric cancer cell line. J Mol Struct 2020; 1208: 127889.
Mortazavi-Derazkola S, Ebrahimzadeh MA, Amiri O. et al. Facile green synthesis and characterization of Crataegus microphylla extract-capped silver nanoparticles (CME@Ag-NPs) and its potential antibacterial and anticancer activities against AGS and MCF-7 human cancer cells. J Alloys Compd 2020; 820: 153186.
Aslany S, Tafvizi F, Naseh V. Characterization and evaluation of cytotoxic and apoptotic effects of green synthesis of silver nanoparticles using Artemisia Ciniformis on human gastric adenocarcinoma. Mater Today Commun 2020; 24: 101011.
Li C, Zhang Y, Li M, Zhang H, Zhu Z, Xue Y. Fumaria officinalisassisted synthesis of Manganese nanoparticles as an anti-human gastric cancer agent. Arab J Chem 2021; 14(10): 103309.
Yuan X, He Y, Zhou G, Li X, Feng A, Zheng W. Target challenging-cancer drug delivery to gastric cancer tissues with a fucose graft epigallocatechin-3-gallate-gold particles nanocomposite approach. J Photochem Photobiol B 2018; 183: 147-53.
[ ] [PMID: 29705507]
Batooei S, Khajeali A, Khodadadi R, Pirayesh Islamian J. Metal-based nanoparticles as radio-sensitizer in gastric cancer therapy. J Drug Deliv Sci Technol 2020; 56: 101576.
Lai C-K, Lu Y-L, Hsieh J-T. et al. Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric can-cer therapy. Nanomedicine (Lond) 2014; 9(6): 803-17.
[ ] [PMID: 24024568]
Amin A, Awad B. Crocin-Sorafenib combination therapy for liver cancer. US10933076B2. 2021.
Amin A. Prevention of liver cancer with Safranal-based formulations. US10912741B2. 2020.
Amin A, Almansoori A, Baig B. Safranal-sorafenib combination therapy for liver cancer. Safranal-sorafenib combination therapy for liver cancer US10568873B1., 2020.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy