Epithelial-mesenchymal transition(EMT),the transdifferentiation of epithelial cells into mesenchymal cells,has been reported to play an important role in the cancer cells metastasis and provides novel strategies for cancer therapy.Toosendanin(TSN),a triterpenoid derivative extracted from Melia toosendan Sieb et Zucc,has been reported to have anti-cancer effect through inducing apoptosis in several lines of cancer cells.In this study,we reported that TSN inhibited TGF-β1-induced EMT in A549 cells.Cells were treated with TGF-β1 to induce EMT.The effect of TSN(0-20 nM)was studied.The morphological alterations were observed with a microscopy.The protein expression of EMT markers was determined by Western blotting and the protein localization was detected by immunofluorescence.The migration,invasion,and adhesion were observed by wound-healing,Transwell,and adhesion assays respectively.Results showed that TGF-β1 treatment induced spindle-shaped alterations of cells,upregulation of N-cadherin,Vimentin,phosphor-ERK,and downregulation of E-cadherin.TSN also increased abilities of cell migration,invasion,and adhesion.These effects were dramatically reversed by TSN.Furthermore,PD98059 and U0125,two ERK inhibitors,showed similar effects.In summary,TSN inhibited TGF-β1-induced EMT and cells migration,invasion,and adhesion through ERK pathway in human lung cancer A549 cells.This study provides new insight for effect and novel molecular mechanisms for TSN in cancer treatment.