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

Siddharth J Modi; Anshuly Tiwari; Vithal M Kulkarni

doi:10.1016/j.crphar.2021.100014

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

Curr Res Pharmacol Drug Discov. 2021 Jan 19:2:100014. doi: 10.1016/j.crphar.2021.100014. eCollection 2021.

Authors

Siddharth J Modi¹, Anshuly Tiwari¹, Vithal M Kulkarni¹

Affiliation

¹ Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, 411038, Maharashtra, India.

Abstract

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.

Keywords: E-cadherin; Epithelial–mesenchymal transition; SNAIL; Sorafenib; Vimentin.