Transforming growth factor-β1 contributes to oxaliplatin resistance in colorectal cancer via epithelial to mesenchymal transition

Abstract

Transforming growth factor-β1 (TGF-β1), secreted by main components of tumor microenvironment, is consid-ered to be closely associated with cancer development and chemoresistance. The present study aimed to analyze the effects and mechanisms underlying TGF-β1-induced chemoresistance to oxaliplatin (LOH) in human colorectal cancer (CRC) cell lines. The cytotoxic effects of LOH subsequent to TGF-β1 treatment were assessed in three CRC cell lines by MTT assay. In addition, epithelial to mesenchymal transition (EMT), DNA damage and apoptosis assays were performed to evaluate the mechanisms of drug resistance in vitro. It was revealed that an exposure of CRC cells to TGF-β1 induced EMT. This was followed by a decrease in the levels of DNA damage and LOH-induced apoptotic cell death at certain TGF-β1 concentrations compared with untreated cells, which was responsible for LOH resistance. TGF-β1 leads to resistance to LOH in CRC cells, primarily through EMT. These data not only provide insight into the understanding of the chemoresistant mechanisms, but also may guide the clinical applications of reducing EMT to enhance the sensitivity to chemotherapy, by targeting TGF-β1.