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

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.