Evaluation of Changes in the Expression Profile of mRNA and Proteinencoding Adiponectin in Ishikawa Cell Line under the Influence of Cisplatin – Preliminary Report

Author(s): Robert Kiełabsiński*, Przemysław Kieszkowski, Beniamin O. Grabarek, Dariusz Boroń

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 12 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: A reduced concentration of adiponectin is considered as an independent factor of the risk of inducing endometrial cancer. Cisplatin is a drug used in the therapy of this type of neoplasm. However, knowledge of the effects of cisplatin on the adiponectin level is still limited.

Objective: The purpose of this study was to assess the impact of cisplatin depending on the concentration and time of exposition of the cells to the drug on the adiponectin level in the endometrial cancer cell line.

Methods: Cells of endometrial cancer cell line Ishikawa were exposed for 12,24 and 48 hour periods to cisplatin with the following concentrations: 2.5μM, 5μM, 10μM. The changes in the expression profile of adiponectin were compared to the RtqPCR reaction and ELISA test. The STATISTICA 13.0 PL program was used for statistical analysis (p<0.05).

Results: In the culture without the drug, the concentration of adiponectin was statistically lower than in the cell culture incubated with the drug. Changes on the mRNA level seem to be more specific than on the protein level, although in both cases, the same trend in the expression changes was noted.

Discussion: The longer the time of exposition of the cells to the drug, the expression of mRNA, and the adiponectin protein increased. Changes in the expression profile were characterized statistically (p<0.05).

Conclusion: Cisplatin, in a noticeable way, changes the expression profile of adiponectin. Molecular analysis indicated that in the case of endometrial cancer therapy should be implemented with a concentration of no less than 5 μM.

Keywords: Adiponectin, Ishikawa cell line, molecular marker, cisplatin, endometrial cancer, cisplatin.

[1]
Schuster, S.; Cabrera, D.; Arrese, M.; Feldstein, A.E. Triggering and resolution of inflammation in NASH. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(6), 349-364.
[http://dx.doi.org/10.1038/s41575-018-0009-6 ] [PMID: 29740166]
[2]
Tsochatzis, E.; Papatheodoridis, G.V.; Archimandritis, A.J. The evolving role of leptin and adiponectin in chronic liver diseases. Am. J. Gastroenterol., 2006, 101(11), 2629-2640.
[http://dx.doi.org/10.1111/j.1572-0241.2006.00848.x] [PMID: 16952281]
[3]
Ezzidi, I.; Mtiraoui, N.; Mohmmed Ali, M.E.; Al Masoudi, A.; Abu Duhier, F. Adiponectin (ADIPOQ) gene variants and haplotypes in Saudi Arabian women with Polycystic Ovary Syndrome (PCOS): A case-control study Gynecol. Endocrinol., 2020, 36(1), 66-71.
[http://dx.doi.org/10.1080/09513590.2019.1632830] [PMID: 31242787]
[4]
Yanai, H.; Yoshida, H.; Iseli, T.J. Beneficial effects of adiponectin on glucose and lipid metabolism and atherosclerotic progression; Mechanisms and perspectives. Int. J. Mol. Sci., 2019, 20(5), 1190.
[http://dx.doi.org/10.3390/ijms20051190 ] [PMID: 30857216]
[5]
Dong, Z.; Su, L.; Esmaili, S.; Iseli, T.J.; Ramezani-Moghadam, M.; Hu, L.; Xu, A.; George, J.; Wang, J. Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells. J. Mol. Med. (Berl.), 2015, 93(12), 1327-1339.
[http://dx.doi.org/10.1007/s00109-015-1313-z ] [PMID: 26153548]
[6]
Nepal, S.; Park, P.H. Modulation of cell death and survival by adipokines in the liver. Biol. Pharm. Bull., 2015, 38(7), 961-965.
[http://dx.doi.org/10.1248/bpb.b15-00188 ] [PMID: 26133703]
[7]
Ruan, H.; Dong, L.Q. Adiponectin signaling and function in insulin target tissues. J. Mol. Cell Biol., 2016, 8(2), 101-109.
[http://dx.doi.org/10.1093/jmcb/mjw014 ] [PMID: 26993044]
[8]
Pagano, C.; Soardo, G.; Esposito, W.; Fallo, F.; Basan, L.; Donnini, D.; Federspil, G.; Sechi, L.A.; Vettor, R. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur. J. Endocrinol., 2005, 152(1), 113-118.
[http://dx.doi.org/10.1530/eje.1.01821 ] [PMID: 15762194]
[9]
Musso, G.; Gambino, R.; De Michieli, F.; Premoli, A.; Biroli, G.; Fagà, E.; Durazzo, M. The postprandial phase as a link between systemic lipid peroxidation and liver injury in NASH. Am. J. Gastroenterol., 2006, 101, 1-9.
[http://dx.doi.org/10.1111/j.1572-0241.2006.00794.x]
[10]
Kobayashi, H.; Ouchi, N.; Kihara, S.; Walsh, K.; Kumada, M.; Abe, Y.; Funahashi, T.; Matsuzawa, Y. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ. Res., 2004, 94(4), e27-e31.
[http://dx.doi.org/10.1161/01.RES.0000119921.86460.37] [PMID: 14752031]
[11]
Xu, A.; Wang, Y.; Keshaw, H.; Xu, L.Y.; Lam, K.S.; Cooper, G.J. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J. Clin. Invest., 2003, 112(1), 91-100.
[http://dx.doi.org/10.1172/JCI200317797 ] [PMID: 12840063]
[12]
Nishida, M.; Kasahara, K.; Oki, A.; Satoh, T.; Arai, Y.; Kubo, T. Establishment of eighteen clones of Ishikawa cells. Hum. Cell, 1996, 9(2), 109-116.
[PMID: 9183638]
[13]
Straub, L.G.; Scherer, P.E. Metabolic messengers; adiponectin. Nat. Metabolism, 2019, 1(3), 334-339.
[http://dx.doi.org/10.1038/s42255-019-0041-z]
[14]
Di Zazzo, E.; Polito, R.; Bartollino, S. Nigro; E.; Porcile, C.; Bianco, A.; Moncharmont, B. adiponectin as link factor between adipose tissue and cancer. Int. J. Mol. Sci., 2019, 20(4), 839.
[http://dx.doi.org/10.3390/ijms20040839]
[15]
Rinaldi, G.; Rossi, M.; Fendt, S.M. Metabolic interactions in cancer: cellular metabolism at the interface between the microenvironment, the cancer cell phenotype and the epigenetic landscape. Wiley Interdiscip. Rev. Syst. Biol. Med., 2018, 10(1)e1397
[http://dx.doi.org/10.1002/wsbm.1397 ] [PMID: 28857478]
[16]
Turgeon, M.O.; Perry, N.J.S.; Poulogiannis, G. DNA damage; repair; and cancer metabolism. Front. Oncol., 2018, 8, 15.
[http://dx.doi.org/10.3389/fonc.2018.00015 ] [PMID: 29459886]
[17]
Kölbl, A.C.; Birk, A.E.; Kuhn, C.; Jeschke, U.; Andergassen, U. Influence of VEGFR and LHCGR on endometrial adenocarcinoma. Oncol. Lett., 2016, 12(3), 2092-2098.
[http://dx.doi.org/10.3892/ol.2016.4906 ] [PMID: 27625708]
[18]
Randall, M.E.; Filiaci, V.L.; Muss, H.; Spirtos, N.M.; Mannel, R.S.; Fowler, J.; Thigpen, J.T.; Benda, J.A. Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J. Clin. Oncol., 2006, 24(1), 36-44.
[http://dx.doi.org/10.1200/JCO.2004.00.7617 ] [PMID: 16330675]
[19]
Manohar, S.; Leung, N. Cisplatin nephrotoxicity: A review of the literature. J. Nephrol., 2018, 31(1), 15-25.
[http://dx.doi.org/10.1007/s40620-017-0392-z ] [PMID: 28382507]
[20]
Brinton, L.A.; Berman, M.L.; Mortel, R.; Twiggs, L.B.; Barrett, R.J.; Wilbanks, G.D.; Lannom, L.; Hoover, R.N. Reproductive, menstrual, and medical risk factors for endometrial cancer: Results from a case-control study. Am. J. Obstet. Gynecol., 1992, 167(5), 1317-1325.
[http://dx.doi.org/10.1016/S0002-9378(11)91709-8 ] [PMID: 1442985]
[21]
Moon, H.S.; Chamberland, J.P.; Aronis, K.; Tseleni-Balafouta, S.; Mantzoros, C.S. Direct role of adiponectin and adiponectin receptors in endometrial cancer: In vitro and ex vivo studies in humans. Mol. Cancer Ther., 2011, 10(12), 2234-2243.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0545] [PMID: 21980131]
[22]
Cai, Z.F.; Deng, L.; Wang, M.M.; Zhang, J.Q.; Li, L. Effect of AMPK/mTOR/S6K1 pathways and the insulin-sensitizing effect for adiponectin in endometrial cancer cells. Zhonghua Fu Chan Ke Za Zhi, 2018, 53(8), 554-560.
[PMID: 30138966]
[23]
Körner, A.; Pazaitou-Panayiotou, K.; Kelesidis, T.; Kelesidis, I.; Williams, C.J.; Kaprara, A.; Bullen, J.; Neuwirth, A.; Tseleni, S.; Mitsiades, N.; Kiess, W.; Mantzoros, C.S. Total and high-molecular-weight adiponectin in breast cancer: In vitro and in vivo studies. J. Clin. Endocrinol. Metab., 2007, 92(3), 1041-1048.
[http://dx.doi.org/10.1210/jc.2006-1858 ] [PMID: 17192291]
[24]
Chitcholtan, K.; Sykes, P.H.; Evans, J.J. The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer. J. Transl. Med., 2012, 10(1), 38.
[http://dx.doi.org/10.1186/1479-5876-10-38 ] [PMID: 22394685]
[25]
Wang, Z.; Gao, S.; Sun, C.; Li, J.; Gao, W.; Yu, L. Clinical significance of serum adiponectin and visfatin levels in endometrial cancer. Int. J. Gynaecol. Obstet., 2019, 145(1), 34-39.
[http://dx.doi.org/10.1002/ijgo.12772 ] [PMID: 30702161]
[26]
Gong, T.T.; Wu, Q.J.; Wang, Y.L.; Ma, X.X. Circulating adiponectin, leptin and adiponectin-leptin ratio and endometrial cancer risk: Evidence from a meta-analysis of epidemiologic studies. Int. J. Cancer, 2015, 137(8), 1967-1978.
[http://dx.doi.org/10.1002/ijc.29561 ] [PMID: 25899043]
[27]
Ciortea, R.Ă.Z. V A.N., Şuşman; S.; Măluţan, A.M.; Berceanu, C.; Mocan-Hognogi, R. F.; Bucuri, C.E.; Mihu, D. Mesenchymal stem cells derived from adipose tissue and Ishikawa cells co-culture highlight the role of adiponectin in endometrial cancer pathogenesis. Romanian journal of morphology and embryology. Rev. Roum. Morphol. Embryol., 2018, 59(4), 1165-1172.
[28]
Bråkenhielm, E.; Veitonmäki, N.; Cao, R.; Kihara, S.; Matsuzawa, Y.; Zhivotovsky, B.; Funahashi, T.; Cao, Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc. Natl. Acad. Sci. USA, 2004, 101(8), 2476-2481.
[http://dx.doi.org/10.1073/pnas.0308671100 ] [PMID: 14983034]
[29]
Maleki, M.; Ghanbarvand, F.; Reza Behvarz, M.; Ejtemaei, M.; Ghadirkhomi, E. Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int. J. Stem Cells, 2014, 7(2), 118-126.
[http://dx.doi.org/10.15283/ijsc.2014.7.2.118 ] [PMID: 25473449]
[30]
Alhazzani, K.; Alaseem, A.; Algahtani, M.; Dhandayuthapani, S.; Venkatesan, T.; Rathinavelu, A. angiogenesis in cancer treatment; 60 years’ swing between promising trials and disappointing tribulations. Anti-Angiogen. Drug Discov. Developm., 2019, 4(4), 34.
[http://dx.doi.org/10.2174/9781681083971119040005]
[31]
Busch, C.J.; Becker, B.; Kriegs, M.; Gatzemeier, F.; Krüger, K.; Möckelmann, N.; Fritz, G.; Petersen, C.; Knecht, R.; Rothkamm, K.; Rieckmann, T. Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines. Oncotarget, 2016, 7(24), 35832-35842.
[http://dx.doi.org/10.18632/oncotarget.9028 ] [PMID: 27127883]
[32]
Skolekova, S.; Matuskova, M.; Bohac, M.; Toro, L.; Durinikova, E.; Tyciakova, S.; Demkova, L.; Gursky, J.; Kucerova, L. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells. Cell Commun. Signal., 2016, 14(1), 4.
[http://dx.doi.org/10.1186/s12964-016-0127-0 ] [PMID: 26759169]


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 12
Year: 2020
Published on: 05 May, 2020
Page: [1242 - 1248]
Pages: 7
DOI: 10.2174/1389201021666200506074523

Article Metrics

PDF: 29
HTML: 2
EPUB: 1
PRC: 1