Oxymatrine inhibits the migration of human colorectal carcinoma RKO cells via inhibition of PAI-1 and the TGF-β1/Smad signaling pathway

Transforming growth factor-β1 (TGF-β1) signaling has been shown to play a critical role in the development of epithelial-mesenchymal transition (EMT). PAI-1 is one of the most important target genes in the TGF-β/Smad signaling pathway, which can hinder the degradation of ECM composition and may promote cell invasion and migration. Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora flavescens Ait and has been demonstrated to inhibit the growth of various types of cancer cells including colorectal cancer. However, the anticancer effect of OM in colorectal cancer remains unclear. In the present study, we detected the expression of E-cadherin, α-SMA, FN, TGF-β1, PAI-1, Smad4, pP38 and pSmad2 in FHC, RKO and OM-treated RKO cells. We also detected pSmad2 and PAI-1 in RKO cells following the addition of SB203580 (a p38 MAPK inhibitor). The results showed that E-cadherin expression in RKO cells was significantly decreased, while PAI-1, TGF-β1, α-SMA, FN, Smad4, pSmad2 and pP38 expression levels were significantly increased in the RKO cells compared to levels in the FHC cells, which was almost completely reversed by OM. OM alleviated EMT induced in colorectal cancer via inhibition of TGF-β1/Smad signaling pathway activation by reducing P38-dependent increased expression of PAI-1. Hence, OM could be a novel therapeutic agent for colorectal cancer.