Abstract
Epithelial-to-mesenchymal transition (EMT) is an essential phenotypic conversion involved in cancer progression. Epidermal growth factor (EGF) and transforming growth factor (TGF)-β1 are potent inducers of the EMT. Tanshinone IIA (Tan IIA) is a phenanthrenequinone extracted from the root of Salvia miltiorrhiza Bunge, and its anticancer activity has been demonstrated in numerous studies. However, the mechanisms of action underlying Tan IIA in EGF- and TGF-β1-induced EMT in HepG2 cells remain unknown. Multiple assays were utilized in the present study, including colony formation, wound healing, Transwell invasion, immunofluorescence staining and western blotting, in order to assess the influence of Tan IIA on HepG2 cells induced by 20 ng/ml EGF and 10 ng/ml TGF-β1. The present study reported that Tan IIA treatment decreased EGF- and TGF-β1-enhanced cell colony numbers, migration and invasion, and inhibited EGF- and TGF-β1-induced decreases in the expression levels of E-cadherin, and increases in the expression levels of matrix metalloproteinase-2, N-cadherin, vimentin and Snail. In addition, it was observed that Tan IIA decreased the expression levels of phosphorylated (p)-Akt and p-ERK1/2 induced by EGF and TGF-β1. Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF- and TGF-β1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF- and TGF-β1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.