Investigate The Relationship Between IGFBP-5 And The Inhibition Effect Of Tetrandrine In Colon Cancer Cells

Colon cancer as one of the most common malignancies, causes considerable morbidity and mortality. The current treatment for colon cancer is more modest than had been hoped. In this study, we investigated the proliferation inhibitory effect of tetrandrine on colon cancer cells and the possible molecular basis underlay this effect. We treated LoVo cells with tetrandrine and then measured the proliferation, apoptosis, and the expression of IGFBP-5. We also employed dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) induced colon cancer model and xenograft colon cancer model to evaluate the effect of tetrandrine on colon cancer. Finally, we introduced luciferase reporter assay, recombinant adenovirus mediated expression of IGFBP-5, IGFBP-5 small interference RNAs, p53, and mutant p53 to analysis the possible mechanism behind the function of terandrine. It showed that tetrandrine inhibits proliferation and induces apoptosis in LoVo cells, prevents or inhibits DMH and DSS induced aberrant crypt foci (ACF) and colon cancer formation, and suppresses tumor growth in a xenograft colon cancer model. Tetrandrine also down regulates IGFBP-5 but up regulates p53 in LoVo cells. Exogenous expression of IGFBP-5 reverses the inactivation of Wnt/β-catenin signaling by tetrandrine. Exogenous expression of p53 enhances tetrandrine induced IGFBP-5 down regulation, and p53 mutation attenuates this activity of tetrandrine. These results demonstrated that tetrandrine has potential as a chemoprevention and chemotherapeutic agent for colon caner; Tetrandrine inhibits Wnt/β-catenin signaling transduction, which may be mediated by down regulating the expression of IGFBP-5 through a p53 dependent mechanism partly.