Reversal of TGF-β-induced epithelial–mesenchymal transition in hepatocellular carcinoma by sorafenib, a VEGFR-2 and Raf kinase inhibitor

Autor: Siddharth J. Modi, Anshuly Tiwari, Vithal M. Kulkarni
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Current Research in Pharmacology and Drug Discovery, Vol 2, Iss , Pp 100014- (2021)
Druh dokumentu: article
ISSN: 2590-2571
DOI: 10.1016/j.crphar.2021.100014
Popis: The epithelial–mesenchymal transition (EMT) is considered an essential process for cancer development and metastasis. Sorafenib, a RAF kinase and VEGFR-2 inhibitor, exhibits efficacy against advanced hepatocellular carcinoma (HCC), renal carcinoma, and thyroid cancer. It is well established that transforming growth factor-β (TGF-β) activated EMT is involved in the invasion and metastasis of Hep G2 cells in HCC. In this study, we investigated the effects of sorafenib on various biomarkers associated with EMT using flow cytometry. We found that sorafenib upregulated the epithelial marker E-cadherin and downregulated the mesenchymal marker vimentin. Furthermore, sorafenib downregulated the level of the EMT-inducing transcription factor SNAIL. Our findings provide insights into the mechanisms associated with the anti-EMT effects of VEGFR-2/RAF kinase inhibitors.
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