TGF-?1/PTEN/PI3K Signaling Plays An Important Role In The Anti-proliferation Effect Of Tetrandrine In Human Colon Cancer HCT116 Cells

To date,the diagnosis and treatment for colon cancer have been greatly developed,but the prognosis remains unsatisfactory.There is still a great clinical need to explore new efficacious drugs for colon cancer treatment.Tetrandrine(Tet)is an bis-benzylisoquinoline alkaloid.It has been approved that Tet may be a potential candidate for cancer treatment,but the explicit mechanism underlying this activity remains unclear.In this study,we investigated the anti-cancer activity of Tet in human colon cancer cells and dissected the possible mechanism.With crystal violet staining,cell viability assay and flow cytometry analysis,we confirmed that Tet can effectively inhibit the proliferation and induce apoptosis in HCT116 cells.Western blot assay results show that Tet can effectively reduced the protein level of PCNA and Bcl-2 with a concentration manner,but increase the protein level of Bad.Mechanically,we found that Tet greatly increases the mRNA and protein level of TGF-?1 in HCT116 cells.Exogenous TGF-?1 enhances the anti-proliferation and apoptosis inducing effect of Tet in HCT116 cells,which has been partly reversed by TGF-?1 inhibitor.Tet decreases the phosphorylation of Akt1/2/3 in HCT116 cells.This effect can be enhanced by exogenous TGF-?1,but partly reversed by TGF-?1 inhibitor.Tet exhibits no effect on total level of PTEN,but decreases the phosphorylation of PTEN;Exogenous TGF-?1 enhances the effect of Tet on decreasing the phosphorylation of PTEN,which was partly reversed by TGF-?1 inhibitor.Our findings suggested that Tet may be a promising candidate for colon cancer treatment,and the anti-cancer activity may be mediated by inactivating PI3K/Akt signaling through up-regulating TGF-?1 to decrease the phosphorylation of PTEN.