Low-dose cisplatin exposure and SNAIL, Vimentin, E-cadherin expression in HEPG2 cell line
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The publication is free and its contents are distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND 4.0). The rights of the works published in this journal are property of the author and they are free to distribute and disseminate the same sources as long as he correctly cites the font of publication, these acts are not for commercial purposes and no derivative works are generated.
Main Article Content
Abstract
Cisplatin, the first platinum compound approved for cancer treatment, is widely used in the treatment of various cancers including hepatocellular carcinoma (HCC). HCC incidence rates rise globally. Epithelial mesenchymal transition (EMT) is implicated in cancer invasion and metastasis, which are associated with increased mortality. Cisplatin dose might influence cancer invasion and metastatic behavior of the cells. The aim of the study was to investigate the effect of low-dose cisplatin treatment on EMT- related changes in HepG2 cells. Following treatment with 4 µM cisplatin, HepG2 cells were evaluated morphologically. Gene expression of E-cadherin, Vimentin, Snail1 was assessed by quantitative PCR. Immunofluorescence analyses of NA-K ATPase were performed. Although the low-dose cisplatin treated cells exhibited a more stretched morphology, no statistical difference was detected in gene expression of E-cadherin, Vimentin, Snail1 and immunofluorescence of NA-K ATPase. Findings on low-dose cisplatin effects in HepG2 might contribute to the knowledge of antineoplastic inefficacy by further understanding the molecular mechanisms of drug action.
References
Ashrafizadeh, M., Zarrabi, A., Hushmandi, K., Kalantari, M., Mohammadinejad, R., Javaheri, T., Sethi, G. (2020) Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance. Int J Mol Sci., 21(11):2-46, DOI: 10.3390/ijms21114002
Babaei, G., Aziz, S.G-G., Jaghi, N.Z.Z. (2021) EMT, cancer stem cells and autophagy; The three main axes of metastasis. Biomed Pharmacother., 133(110909): 1-11, DOI: 10.1016/j.biopha.2020.110909
Choi, J.E., Bae, J.S., Kang, M.J., Chung, M.J., Jang, K.Y., Park, H.S., Moon, W.S. (2017) Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance. Oncol Rep., 38(3):1695-1705, DOI: 10.3892/or.2017.5790
Dang, H., Ding, W., Emerson, D., Rountree, C.B. (2011) Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics. BMC Cancer, 11(396):1-13, DOI: 10.1186/1471-2407-11-396
Dasari, S., Tchounwou, P.B. (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol., 740:364-378 DOI: 10.1016/j.ejphar.2014.07.025
Donmez Cakıl, Y., Ozunal, Z.G., Gokceoglu Kayalı, D., Aktas, R.G. (2021) The expression of CD44, CD90 and CD133 in response to cisplatin in hepatocellular cancer cells. Eur J Clin Exp Med., 19(1): 18-22, DOI: 10.15584/ejcem.2021.1.3
Fang, S., Yu, L., Mei, H., Yang, J., Gao, T., Cheng, A., Guo, W., Xia, K., Liu, G. (2016) Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail. Oncol Lett., 12(6):5007-5014, DOI: 10.3892/ol.2016.5342
Gurzu, S., Kobori, L., Fodor, D., Jung, I. (2019) Epithelial Mesenchymal and Endothelial Mesenchymal Transitions in Hepatocellular Carcinoma: A Review. BioMed Research International, 2019:1-12, DOI: 10.1155/2019/2962580
Haslehurst, A.M., Koti, M., Dharsee, M., Nuin, P., Evans, K., Geraci, J., Childs, T., Chen, J., Li, J., Weberpals, J., Davey, S., Squire, J., Park, P.C., Feilotter, H. (2012) EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC cancer 12:91, DOI: 10.1186/1471-2407-12-91
Jou, J., Diehl, A.M. (2010) Epithelial-mesenchymal transitions and hepatocarcinogenesis. J Clinic Invest., 120(4):1031-1034, DOI: 10.1172/JCI42615
Kauffman, G., Pentimalli, R., Doldi, S., Hall, M. (2010) Michele Peyrone (1813-1883), Discoverer of Cisplatin. Platinum Metals Review, 54(4):250-256, DOI:10.1595/147106710X534326
Kim, D.W., Talati, C., Kim, R. (2017) Hepatocellular carcinoma (HCC): beyond sorafenib-chemotherapy. J Gastrointest Oncol., 8(2):256-265, DOI: 10.21037/jgo.2016.09.07
Kubala, M., Geleticova, J., Huliciak, M., Zatloukalova, M., Vacek, J., Sebela, M. (2014) Na(+)/K(+)-ATPase inhibition by cisplatin and consequences for cisplatin nephrotoxicity. 158(2):194-200, 10.5507/bp.2014.018
Laface, C., Laforgia, M., Molinari, P., Ugenti, I., Gadaleta, C.D., Porta, C., Ranieri, G. (2021) Hepatic Arterial Infusion of Chemotherapy for Advanced Hepatobiliary Cancers: State of the Art. Cancers, 13(12):1-23, DOI: 10.3390/cancers13123091
Latifi A, Abubaker K, Castrechini N, Ward AC, Liongue C, Dobill F, Kumar J, Thompson EW, Quinn MA, Findlay, J.K., Ahmed, N. (2011) Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile. J Cell Biochem., 112(10):2850-2864, DOI: 10.1002/jcb.23199
Liu, X., Huang, H., Remmers, N., Hollingsworth, M.A. (2014) Loss of E-cadherin and epithelial to mesenchymal transition is not required for cell motility in tissues or for metastasis. Tissue Barriers, 2(4):e969112, DOI: 10.4161/21688362.2014.969112
Myong, N.H. (2012) Loss of E-cadherin and Acquisition of Vimentin in Epithelial-Mesenchymal Transition are Noble Indicators of Uterine Cervix Cancer Progression. Korean J Pathol., 46(4):341-348, DOI: 10.4132/KoreanJPathol.2012.46.4.341
Niknami, Z., Muhammadnejad, A., Ebrahimi, A., Harsani, Z., Shirkoohi, R. (2020) Significance of E-cadherin and Vimentin as epithelial-mesenchymal transition markers in colorectal carcinoma prognosis. EXCLI J., 19:917-926, DOI: 10.17179/excli2020-1946
Nilsson, G.M., Akhtar, N., Kannius-Janson, M., Baeckström, D. (2014) Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition. Int J Oncol., 45(1):82-94, DOI: 10.3892/ijo.2014.2424
Rajasekaran, S.A., Huynh, T.P., Wolle, D.G., Espineda, C.E., Inge, L.J., Skay, A., Lassman, C., Nicholas, S.B., Harper, J.F., Reeves, A.E., Ahmed, M.M., Leatherman, J.M., Mullin, J.M., Rajasekaran, A.K. (2010) Na,K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis. Mol Cancer Ther., 9(6):1515-1524, DOI: 10.1158/1535-7163.MCT-09-0832
Rosenberg, B., VanCamp, L., Trosko, J.E., Mansour, V.H. (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222(5191):385-386, DOI: 10.1038/222385a0.
Satelli, A., Li, S. (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci., CMLS 68(18):3033-3046, DOI: 10.1007/s00018-011-0735-1
Schneider, V., Krieger, M.L., Bendas, G., Jaehde, U., Kalayda, G.V. (2013) Contribution of intracellular ATP to cisplatin resistance of tumor cells. J Biol Inor Chem., 18(2):165-74, DOI: 10.1007/s00775-012-0960-6
Šeflová, J., Čechová, P., Štenclová, T., Šebela, M., Kubala, M. (2018) Identification of cisplatin-binding sites on the large cytoplasmic loop of the Na+/K+-ATPase. J Enzyme Inhib Med Chem., 33(1):701-706, DOI: 10.1080/14756366.2018.1445735
Seo, J., Ha, J., Kang, E., Cho, S. (2021) The role of epithelial–mesenchymal transition-regulating transcription factors in anti-cancer drug resistance. Arch Pharm Res., 44(3):281-292, DOI: 10.1007/s12272-021-01321-x
Su, Z., Li, G., Liu, C., Ren, S., Deng, T., Zhang, S., Tian, Y., Liu, Y., Qiu, Y. (2017) Autophagy inhibition impairs the epithelial-mesenchymal transition and enhances cisplatin sensitivity in nasopharyngeal carcinoma.
Oncol Lett., 13(6):4147-4154, DOI: 10.3892/ol.2017.5963
Tanabe, S., Quader, S., Cabral, H., Ono, R. (2020) Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies. Front Parmacol., 17(11):1-8, DOI: 10.3389/fphar.2020.00904
Woo, H.Y., Min, A.L., Choi, J.Y., Bae, S.H., Yoon, S.K., Jung, C.K. (2011) Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma. Korean J Hepatol., 17(1):12-18, DOI: 10.3350/kjhep.2011.17.1.12
Yang, J., Antin, P., Berx, G., Blanpain, C., Brabletz, T., Bronner, M., Campbell, K., Cano, A., Casanova, J., Christofori, G., On behalf of the EMTIA (2020). Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol., 21(6):341-352, DOI: 10.1038/s41580-020-0237-9
Zhang, H., Chang, W.J., Li, X.Y., Zhang, N., Kong, J.J., Wang, Y.F. (2014) Liver cancer stem cells are selectively enriched by low-dose cisplatin. Braz J Med Biol Res., 47(6):478-482, DOI: 10.1590/1414-431X20143415