NT5E inhibition suppresses the growth of sunitinib-resistant cells and EMT course and AKT/GSK-3β signaling pathway in renal cell cancer

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Abstract

We aimed to explore the mechanisms of sunitinib-resistance in renal cell cancer (RCC) and provide new therapeutic evidence and biomarkers for RCC treatment using human clear-cell renal cell carcinoma (ccRCC) cell line, 786-O. Microarray analysis, quantitative real time PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect Ecto-5′-nucleotidase (NT5E) expressions in sunitinib-resistant tissues in RCC. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT), cell-count kit 8 (CCK-8), wound healing, and Transwell assays were used to investigate the influences of sunitinib and NT5E on 786-O cell line and sunitinib-resistant 786-O cell line (S786-O). Protein expressions related to epithelial–mesenchymal transition (EMT) and AKT/GSK-3β signaling pathway in 786-O cells and S786-O cells were determined by Western blot. In vivo experiment was performed using NCr-nu/nu mice to explore the effects of NT5E on cell growth and EMT signal in sunitinib environment. NT5E expression was upregulated in sunitinib-resistant RCC tissues and cells. NT5E downregulation repressed RCC cell proliferation, migration as well as invasion. EMT course and AKT/GSK-3β signal pathway both in vitro and in vivo in sunitinib environment was suppressed to varying degrees via NT5E inhibition. NT5E inhibition could suppress the growth of sunitinib-resistant RCC cells and restrain EMT course and AKT/GSK-3β signal pathway in sunitinib environment in RCC. © 2018 IUBMB Life, 71(1):113–124, 2019.

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Peng, D., Hu, Z., Wei, X., Ke, X., Shen, Y., & Zeng, X. (2019). NT5E inhibition suppresses the growth of sunitinib-resistant cells and EMT course and AKT/GSK-3β signaling pathway in renal cell cancer. IUBMB Life, 71(1), 113–124. https://doi.org/10.1002/iub.1942

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