Bevacizumab and anexelekto inhibitor, TP-0903 inhibits TGF-β1-induced epithelial-mesenchymal transition of colon cancer cells

Abstract

The incidence of colorectal cancer (CRC) is reported to be increasing nowadays, with a large proportion of newly diagnosed CRC patients being affected by metastasis. Epithelial–mesenchymal transition (EMT) is an important event in the development of metastasis of CRC. In this study, we investigated whether the anticancer drug bevacizumab and anexelekto inhibitor, TP-0903, regulate EMT of colon cancer cells induced by transforming growth factor-beta 1 (TGF-β1). Using quantitative real-time PCR and western blot analysis, we found that bevacizumab and TP-0903 decreased the expression levels of fibronectin, alpha-smooth muscle actin, and vimentin, whereas they restored E-cadherin expression in TGF-β1-exposed SW480 and HCT116 cells. In addition, we elucidated that bevacizumab and TP-0903 inhibited the migration and invasion of TGF-β1-exposed colon cancer cells using scratched wound healing, transwell migration, and Matrigel-coated invasion assays. Finally, we discovered that bevacizumab and TP-0903 inactivated the Smad 2/3 signaling pathway in TGF-β1-exposed SW480 and HCT116 cells. Therefore, we suggest that treatment of bevacizumab and TP-0903 inhibits TGF-β1-induced EMT of colon cancer cells through inactivation of the Smad 2/3 signaling pathway.