Review Article

The Impact of Statin Therapy on the Survival of Patients with Gastrointestinal Cancer

Author(s): Meysam Gachpazan, Hoda Kashani, Majid Khazaei, Seyed Mahdi Hassanian, Majid Rezayi, Fereshteh Asgharzadeh, Majid Ghayour-Mobarhan, Gordon A. Ferns and Amir Avan*

Volume 20, Issue 7, 2019

Page: [738 - 747] Pages: 10

DOI: 10.2174/1389450120666181211165449

Price: $65

Abstract

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins affect several potential pathways, including cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk.

Keywords: Statins, survival of patients, gastrointestinal cancer, angiogenesis, biological mechanisms, statin therapy.

Graphical Abstract
[1]
Herrero R, Park JY, Forman D. The fight against gastric cancer–the IARC Working Group report. Best Pract Res Clin Gastroenterol 2014; 28(6): 1107-14.
[2]
Rebecca M, Thomas MD, Leslie H, Sobin MD. Gastrointestinal cancer. Cancer 1995; 75(S1): 154-70.
[3]
Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110(2): 223-62.
[4]
Lello E, Furnes B, Edna TH. Short and long-term survival from gastric cancer. A population-based study from a county hospital during 25 years. Acta Oncol 2007; 46(3): 308-15.
[5]
Tahara E. Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. Cancer 1995; 75(S6): 1410-7.
[6]
Shu L, Cheung KL, Khor TO, Chen C, Kong AN. Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis. Cancer Metastasis Rev 2010; 29(3): 483-502.
[7]
Singh BN, Singh HB, Singh A, Naqvi AH, Singh BR. Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade. Cancer Metastasis Rev 2014; 33(1): 41-85.
[8]
Järvinen R, Knekt P, Hakulinen T, Rissanen H, Heliövaara M. Dietary fat, cholesterol and colorectal cancer in a prospective study. Br J Cancer 2001; 85(3): 357-61.
[9]
Silvente-Poirot S, Poirot M. Cholesterol and Cancer, in the Balance. Science 2014; 343(6178): 1445-6.
[10]
Chiu HF, Ho SC, Chang CC, Wu TN, Yang CY. Statins are associated with a reduced risk of gastric cancer: a population-based case–control study. Am J Gastroenterol 2011; 106(12): 2098-103.
[11]
Khurana V, Sheth A, Caldito G, Barkin JS. Statins reduce the risk of pancreatic cancer in humans: a case-control study of half a million veterans. Pancreas 2007; 34(2): 260-5.
[12]
Osmak M. Statins and cancer: current and future prospects. Cancer Lett 2012; 324(1): 1-12.
[13]
Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 2010; 9(4): 603-21.
[14]
Kuoppala J, Lamminpää A, Pukkala E. Statins and cancer: A systematic review and meta-analysis. Eur J Cancer 2008; 44(15): 2122-32.
[15]
Singh PP, Singh S. Statins are associated with reduced risk of gastric cancer: a systematic review and meta-analysis. Ann Oncol 2013; 24(7): 1721-30.
[16]
Sattar N, Preiss D, Murray HM. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375(9716): 735-42.
[17]
Nissen SE, Tuzcu EN, Schoenhagen P. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352(1): 29-38.
[18]
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003; 289(13): 1681-90.
[19]
Endo A, Tsujita Y, Kuroda M, Tanzawa K. Inhibition of cholesterol synthesis in vitro and in vivo by ML‐236A and ML‐236B, competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl‐coenzyme a reductase. Eur J Biochem 1977; 77(1): 31-6.
[20]
Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988; 319(1): 24-33.
[21]
Gazzerro P, Proto MC, Gangemi G, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev 2011; 64(1): 102-46.
[22]
Diomede L, Albani D, Sottocorno M, et al. In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. Arterioscler Thromb Vasc Biol 2001; 21(8): 1327-32.
[23]
Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, et al. Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res 2010; 106(2): 297-306.
[24]
Rebecchi IM, Rodrigues AC, Arazi SS, et al. ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment. Biochem Pharmacol 2009; 77(1): 66-75.
[25]
Generaux GT, Bonomo FM, Johnson M, Doan KM. Impact of SLCO1B1 (OATP1B1) and ABCG2 (BCRP) genetic polymorphisms and inhibition on LDL-C lowering and myopathy of statins. Xenobiotica 2011; 41(8): 639-51.
[26]
Pellecchia M, Sem DS, Wüthrich K. NMR in drug discovery. Nat Rev Drug Discov 2002; 1(3): 211-9.
[27]
Dev J, Park D, Fu Q, et al. Structural basis for membrane anchoring of HIV-1 envelope spike. Science 2016; 353(6295): 172-5.
[28]
Schnell JR, Chou JJ. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 2008; 451(7178): 591-5.
[29]
Berardi MJ, Shih WM, Harrison SC, Chou JJ. Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching. Nature 2011; 476(7358): 109-13.
[30]
OuYang B. Xie S, Berardi MJ. Unusual architecture of the p7 channel from hepatitis C virus. Nat 2013; 498(7455): 521-5.
[31]
Oxenoid K, Dong Y, Cao C, et al. Architecture of the mitochondrial calcium uniporter. Nat 2016; 533(7602): 269-73.
[32]
Behroozmand AA, Keating K, Auken E. A review of the principles and applications of the NMR technique for near-surface characterization. Surv Geophys 2015; 36(1): 27-85.
[33]
Chen W, Feng PM, Lin H, Chou KC. iRSpot-PseDNC: identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res 2013; 41(6): e68-8.
[34]
Feng PM, Chen W, Lin H, Chou KC. iHSP-PseRAAAC: Identifying the heat shock protein families using pseudo reduced amino acid alphabet composition. Anal Biochem 2013; 442(1): 118-25.
[35]
Ding H, Deng EZ, Yuan LF, et al. iCTX-Type: A sequence-based predictor for identifying the types of conotoxins in targeting ion channels. BioMed Res Int 2014; 2014: 286419.
[36]
Lin H, Deng EZ, Ding H, Chen W, Chou KC. iPro54-PseKNC: a sequence-based predictor for identifying sigma-54 promoters in prokaryote with pseudo k-tuple nucleotide composition. Nucleic Acids Res 2014; 42(21): 12961-72.
[37]
Chen W, Feng P, Ding H, et al. Using deformation energy to analyze nucleosome positioning in genomes. Genomics 2016; 107(2): 69-75.
[38]
Chen W, Feng P, Yang H, et al. iRNA-AI: identifying the adenosine to inosine editing sites in RNA sequences. Oncotarget 2017; 8(3): 4208-17.
[39]
Feng P, Yang H, Ding H, et al. iDNA6mA-PseKNC: Identifying DNA N6-methyladenosine sites by incorporating nucleotide physicochemical properties into PseKNC. Genomics 2019; 111(1): 96-102.
[40]
Chou KC. Some remarks on protein attribute prediction and pseudo amino acid composition. J Theor Biol 2011; 273(1): 236-47.
[41]
Chou KC, Jones D, Heinrikson RL. Prediction of the tertiary structure and substrate binding site of caspase‐8. FEBS Lett 1997; 419(1): 49-54.
[42]
Chou KC, Tomasselli AG, Heinrikson RL. Prediction of the tertiary structure of a caspase‐9/inhibitor complex. FEBS Lett 2000; 470(3): 249-56.
[43]
Chou KC. Insights from modeling three-dimensional structures of the human potassium and sodium channels. J Proteome Res 2004; 3(4): 856-61.
[44]
Chou KC. Insights from modelling the 3D structure of the extracellular domain of α7 nicotinic acetylcholine receptor. Biochem Biophys Res Commun 2004; 319(2): 433-8.
[45]
Chou KC. Structural bioinformatics and its impact to biomedical science. CMC 2004; 11(16): 2105-34.
[46]
Martin G1, Duez H, Blanquart C, et al. Statin-induced inhibition of the Rho-signaling pathway activates PPARα and induces HDL apoA-I. J Clin Invest 2001; 107(11): 1423-32.
[47]
Amet T, Nonaka M, Dewan MZ, et al. Statin-induced inhibition of HIV-1 release from latently infected U1 cells reveals a critical role for protein prenylation in HIV-1 replication. Microbes Infect 2008; 10(5): 471-80.
[48]
Tleyjeh IM, Kashour T, Hakim FA, et al. Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 2009; 169(18): 1658-67.
[49]
Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6(12): 1399-402.
[50]
Bellosta S, Via D, Canavesi M, et al. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol 1998; 18(11): 1671-8.
[51]
Neuhaus O, Strasser-Fuchs S, Fazekas F, et al. Statins as immunomodulators comparison with interferon-β1b in MS. Neurol 2002; 59(7): 990-7.
[52]
Cheng X, Xiao X, Chou KC. pLoc-mPlant: predict subcellular localization of multi-location plant proteins by incorporating the optimal GO information into general PseAAC. Mol Biosyst 2017; 13(9): 1722-7.
[53]
Cheng X, Xiao X, Chou KC. pLoc-mVirus: predict subcellular localization of multi-location virus proteins via incorporating the optimal GO information into general PseAAC. Gene 2017; 628: 315-21.
[54]
Zhao SG, Lin WZ, Xiao X, Chou KC. pLoc-mAnimal: predict subcellular localization of animal proteins with both single and multiple sites. Bioinformatics 2017; 33(22): 3524-31.
[55]
Xuan X, Cheng X, Su S, Qi M. pLoc-mGpos: incorporate key gene ontology information into general PseAAC for predicting subcellular localization of Gram-positive bacterial proteins. Nat Sci 2017; 9(09): 330-49.
[56]
Cheng X, Xiao X, Chou KC. pLoc-mEuk: Predict subcellular localization of multi-label eukaryotic proteins by extracting the key GO information into general PseAAC. Genomics 2018; 110(1): 50-8.
[57]
Cheng X, Xiao X, Chou KC. pLoc-mGneg: Predict subcellular localization of Gram-negative bacterial proteins by deep gene ontology learning via general PseAAC. Genomics 2018; 110(4): 231-9.
[58]
Cheng X, Xiao X, Chou KC. pLoc-mHum: predict subcellular localization of multi-location human proteins via general PseAAC to winnow out the crucial GO information. Bioinformatics 2017; 34(9): 1448-56.
[59]
Chou KC. Some remarks on predicting multi-label attributes in molecular biosystems. Mol Biosyst 2013; 9(6): 1092-100.
[60]
Lee SJ, Lee I, Lee J, Park C, Kang WK. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, potentiate the anti-angiogenic effects of bevacizumab by suppressing angiopoietin2, BiP, and Hsp90α in human colorectal cancer. Br J Cancer 2014; 111(3): 497-505.
[61]
Zhang P, Wang F, Hu J, Sorrentino R. Label propagation prediction of drug-drug interactions based on clinical side effects. Sci Rep 2015; 5: 12339.
[62]
Xu Y, Shao XJ, Wu LY, Deng NY, Chou KC. iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins. PeerJ 2013; 1: e171.
[63]
Liu B, Yang F, Chou CK. 2L-piRNA: a two-layer ensemble classifier for identifying piwi-interacting RNAs and their function. Mol Ther Nucleic Acids 2017; 7: 267-77.
[64]
Feng P, Ding H, Yang H, et al. iRNA-PseColl: identifying the occurrence sites of different RNA modifications by incorporating collective effects of nucleotides into PseKNC. Mol Ther Nucleic Acids 2017; 7: 155-63.
[65]
Chou KC. Prediction of protein cellular attributes using pseudo‐amino acid composition. Proteins 2001; 43(3): 246-55.
[66]
Chou KC. Pseudo amino acid composition and its applications in bioinformatics, proteomics and system biology. Curr Proteomics 2009; 6(4): 262-74.
[67]
Chen W, Lei TY, Jin DC, Lin H, Chou KC. PseKNC: a flexible web server for generating pseudo K-tuple nucleotide composition. Anal Biochem 2014; 456: 53-60.
[68]
Liu B, Liu F, Wang X. Pse-in-One: a web server for generating various modes of pseudo components of DNA, RNA, and protein sequences. Nucleic Acids Res 2015; 43(W1): W65-71.
[69]
Chou KC. An unprecedented revolution in medicinal chemistry driven by the progress of biological science. CTMC 2017; 17(21): 2337-58.
[70]
Klawitter J, Shokati T, Moll V, Christians U, Klawitter J. Effects of lovastatin on breast cancer cells: a proteo-metabonomic study. Breast Cancer Res 2010; 12(2): R16.
[71]
Poynter J. Rennert G, Bonner JD, et al. HMG CoA reductase inhibitors and the risk of colorectal cancer. J Clin Oncol 2004; 22(14_suppl): 1-1.
[72]
Boudreau DM, Gardner JS, Malone KE, et al. The association between 3‐hydroxy‐3‐methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: A case–control study. Cancer 2004; 100(11): 2308-16.
[73]
Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med 2012; 367(19): 1792-802.
[74]
Brown MS, Goldstein JL. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res 1980; 21(5): 505-17.
[75]
Chan KK, Oza AM, Siu LL, et al. The statins as anticancer agents. Clin Cancer Res 2003; 9(1): 10-9.
[76]
Sivaprasad U, Abbas T, Dutta A. Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer cells. Mol Cancer Ther 2006; 5(9): 2310-6.
[77]
Ukomadu C, Dutta A. p21-dependent inhibition of colon cancer cell growth by mevastatin is independent of inhibition of G1 cyclin-dependent kinases. J Biol Chem 2003; 278(44): 43586-94.
[78]
Agarwal B, Bhendwal S, Halmos B, et al. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res 1999; 5(8): 2223-9.
[79]
Notarnicola M, Messa C, Pricci M, et al. Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left-sided human colon cancer. Anticancer Res 2004; 24(6): 3837-42.
[80]
Bardou M, Barkun A, Martel M. Effect of statin therapy on colorectal cancer. Gut 2010; 59(11): 1572-85.
[81]
Gray RT, Coleman HG, Hughes C, Murray LJ, Cardwell CR. Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis. Cancer Epidemiol 2016; 45: 71-81.
[82]
Poynter JN, Jenny N, Poynter MPH, et al. Statins and the risk of colorectal cancer. N Engl J Med 2005; 352(21): 2184-92.
[83]
Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357(9255): 539-45.
[84]
Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996; 348(9034): 1079-82.
[85]
Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006; 116(7): 1793-801.
[86]
Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353(9157): 983-4.
[87]
Albert MA, Danielson E, Rifai N, Ridker PM, Prince I. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001; 286(1): 64-70.
[88]
Wagner AH, Gebauer M, Güldenzoph B, Hecker M. 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells. Arterioscler Thromb Vasc Biol 2002; 22(11): 1784-9.
[89]
Palinski W. Immunomodulation: a new role for statins? Nat Med 2000; 6(12): 1311.
[90]
Cheng X, Lin WZ, Xiao X, Chou KC. pLoc_bal-mAnimal: predict subcellular localization of animal proteins by balancing training dataset and PseAAC. Bioinformatics 2018; 35(3): 398-406.
[91]
Cheng X, Xiao X, Chou K-C. pLoc_bal-mGneg: predict subcellular localization of Gram-negative bacterial proteins by quasi-balancing training dataset and general PseAAC. J Theor Biol 2018; 458: 92-102.
[92]
Chou K-C, Cheng X, Xiao X. pLoc_bal-mHum: Predict subcellular localization of human proteins by PseAAC and quasi-balancing training dataset. Genomics 2018; pii: S0888-7543(18)30276-3.
[93]
Liu Z, Xiao X, Qiu WR, Chou KC. iDNA-Methyl: Identifying DNA methylation sites via pseudo trinucleotide composition. Anal Biochem 2015; 474: 69-77.
[94]
Jia J, Liu Z, Xiao X, Liu B, Chou KC. iSuc-PseOpt: identifying lysine succinylation sites in proteins by incorporating sequence-coupling effects into pseudo components and optimizing imbalanced training dataset. Anal Biochem 2016; 497: 48-56.
[95]
Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108(3): 391-7.
[96]
Blum CB. Comparison of properties of four inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Am J Cardiol 1994; 73(14): D3-D11.
[97]
Blumenthal RS. Statins: effective antiatherosclerotic therapy. Am Heart J 2000; 139(4): 577-83.
[98]
Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Clin Pharmacokinet 1997; 32(5): 403-25.
[99]
Corsini A, Bellosta S, Baetta R, et al. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999; 84(3): 413-28.
[100]
Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000; 6(9): 1004.
[101]
Mundy G, Garrett R, Harris S, et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999; 286(5446): 1946-9.
[102]
Davignon J, Laaksonen R. Low-density lipoprotein-independent effects of statins. Curr Opin Lipidol 1999; 10(6): 543-59.
[103]
Singh S, Singh AG, Singh PP, Murad MH, Iyer PG. Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11(6): 620-9.
[104]
Wu X-D, Zeng K, Xue FQ, Chen JH, Chen YQ. Statins are associated with reduced risk of gastric cancer: a meta-analysis. Eur J Clin Pharmacol 2013; 69(10): 1855-60.
[105]
You S, Genlin S, Qingchun Y, Zhenzhou W, Xinen H. Statin use and risk of gastrointestinal cancer: a meta-analysis of cohort studies. Int J Clin Exp Med 2018; 11(3): 1437-47.
[106]
Agarwal B, Halmos B, Feoktistov AS, et al. Mechanism of lovastatin-induced apoptosis in intestinal epithelial cells. Carcinogenesis 2002; 23(3): 521-8.
[107]
Cho SJ, Kim JS, Kim JM, et al. Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis‐associated colon cancer in mice. Int J Cancer 2008; 123(4): 951-7.
[108]
Xiao H, Zhang Q, Lin Y, et al. Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer 2008; 122(9): 2115-24.
[109]
West NJ, Courtney ED, Poullis AP, Leicester RJ. Apoptosis in the colonic crypt, colorectal adenomata, and manipulation by chemoprevention. Cancer Epidemiol Biomarkers Prev 2009; 18(6): 1680-7.
[110]
Platz EA, Leitzmann MF, Visvanathan K. Statin drugs and risk of advanced prostate cancer. J Natl Cancer Inst 2006; 98(24): 1819-25.
[111]
Ogunwobi OO, Beales IL. Statins inhibit proliferation and induce apoptosis in Barrett’s esophageal adenocarcinoma cells. Am J Gastroenterol 2008; 103(4): 825.
[112]
Wang IK, Lin‐Shiau SY, Lin JK. Induction of apoptosis by lovastatin through activation of caspase‐3 and DNase II in leukaemia HL‐60 cells. Pharmacol Toxicol 2000; 86(2): 83-91.
[113]
Marcelli M, Cunningham GR, Haidacher SJ, et al. Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. Cancer Res 1998; 58(1): 76-83.
[114]
Cafforio P, Dammacco F, Gernone A, Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis 2005; 26(5): 883-91.
[115]
Hong MY, Seeram NP, Zhang Y, Heber D. Anticancer effects of Chinese red yeast rice versus monacolin K alone on colon cancer cells. J Nutr Biochem 2008; 19(7): 448-58.
[116]
Yang Z, Hang X, Huanyu J, et al. Synergistic actions of atorvastatin with γ‐tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int J Cancer 2010; 126(4): 852-63.
[117]
Denoyelle C, Albanese P, Uzan G, et al. Molecular mechanism of the anti-cancer activity of cerivastatin, an inhibitor of HMG-CoA reductase, on aggressive human breast cancer cells. Cell Signal 2003; 15(3): 327-38.
[118]
Tremblay P-L, Huot J, Auger FA. Mechanisms by which E-selectin regulates diapedesis of colon cancer cells under flow conditions. Cancer Res 2008; 68(13): 5167-76.
[119]
Nubel T, Dippold W, Kleinert H, Kaina B, Fritz G. Lovastatin inhibits Rho-regulated expression of E-selectin by TNFα and attenuates tumor cell adhesion. FASEB 2004; 18(1): 140-2.
[120]
Kusama T, Mukai M, Iwasaki T, et al. 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterol 2002; 122(2): 308-17.
[121]
Ishikawa S, Hayashi H, Kinoshita K, et al. Statins inhibit tumor progression via an enhancer of zeste homolog 2‐mediated epigenetic alteration in colorectal cancer. Int J Cancer 2014; 135(11): 2528-36.
[122]
Kodach LL, Bleuming SA, Peppelenbosch MP, et al. The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway. Gastroenterology 2007; 133(4): 1272-81.
[123]
DeClue JE. DeClue, William C, et al. Inhibition of cell growth by lovastatin is independent of ras function. Cancer Res 1991; 51(2): 712-7.
[124]
Hirai A, Nakamura S, Noguchi Y, et al. Geranylgeranylated rho small GTPase (s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells. J Biol Chem 1997; 272(1): 13-6.
[125]
Rao S, Lowe M, Herliczek TW, Keyomarsi K, et al. Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53. Oncogene 1998; 17(18): 2393.
[126]
Zetterberg A, Larsson O, Wiman KG. What is the restriction point? Curr Opin Cell Biol 1995; 7(6): 835-42.
[127]
Sebti SM, Der CJ. Searching for the elusive targets of farnesyltransferase inhibitors. Nat Rev Cancer 2003; 3(12): 945-51.
[128]
Ridley AJ. Rho family proteins: coordinating cell responses. Trends Cell Biol 2001; 11(12): 471-7.
[129]
Roudier E, Mistafa O, Stenius U. Statins induce mammalian target of rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs. Mol Cancer Ther 2006; 5(11): 2706-15.
[130]
Nishida S, Matsuoka H, Tsubaki M, et al. Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK. Mol Cell Biochem 2005; 269(1): 109-14.
[131]
Li J, Li J-J, He J-G, et al. Atorvastatin decreases c‐reactive protein‐induced inflammatory response in pulmonary artery smooth muscle cells by inhibiting nuclear factor‐κb pathway. Cardiovasc Ther 2010; 28(1): 8-14.
[132]
Chang H-L, Chen CY, Hsu YF, et al. Simvastatin induced HCT116 colorectal cancer cell apoptosis through p38MAPK-p53-survivin signaling cascade. Biochim Biophys Acta 2013; 1830(8): 4053-64.
[133]
Krens LL, Baas JM, Gelderblom H, Guchelaar HJ. Therapeutic modulation of k-ras signaling in colorectal cancer. Drug discov oday 2010; 15(13-14): 502-16.
[134]
Lee J, Lee I, Han B, et al. Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations. J Natl Cancer Inst 2011; 103(8): 674-88.
[135]
Lee J, Hong YS, Hong JY, et al. Effect of simvastatin plus cetuximab/irinotecan for KRAS mutant colorectal cancer and predictive value of the RAS signature for treatment response to cetuximab. Invest New Drugs 2014; 32(3): 535-41.
[136]
Lim S, Kim TW, Hong YS, et al. A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer. B Br J Cancer 2015; 113(10): 1421.
[137]
Dulak J, Józkowicz A. Anti-angiogenic and anti-inflammatory effects of statins: relevance to anti-cancer therapy. Curr Cancer Drug Targets 2005; 5(8): 579-94.
[138]
Tsubaki M, Yamazoe Y, Yanae M, et al. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma. Cytokine 2011; 54(1): 100-7.
[139]
Ortego M, Bustos C, Hernández-Presa MA, et al. Atorvastatin reduces NF-κB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 1999; 147(2): 253-61.
[140]
Neil A, Bustos C, Hernández-Presa MA, et al. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 2008; 29(21): 2625-33.
[141]
Laufs U, Marra D, Node K, Liao JK. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27 Kip1. J Biol Chem 1999; 274(31): 21926-31.
[142]
Bahrami A, Hesari A, Khazaei M, et al. The therapeutic potential of targeting the BRAF mutation in patients with colorectal cancer. J Cell Physiol 2018; 233(3): 2162-9.
[143]
Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, et al. Epigenetic drug therapy in the treatment of colorectal cancer. Curr Pharm Des 2018; 24(23): 2701-9.

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