Study On The Relationship Between The Proliferation Inhibitory Effect Of Ursolic Acid In HCT116 Cells And Wnt/β-catenin

Colon cancer is one of the most common cancers, and ranks the third accounting for the cancer related mortality. The challenges for colon cancer treatment may include the serious adverse effects of chemotherapy drugs and metastasis at least. Although the diagnosis and treatment developed greatly in the last decades, the prognosis remains far below than had been hoped. Hence, there is a great clinical need to exploit new efficacious drugs for colon cancer treatment. Ursolic acid(UA) exhibits anticancer activity in various cancer cells. However, the precise molecular mechanism underlying this processes remains unclear. In this investigation, we demonstrated the anti-proliferation and apoptosis-inducing activities of UA in human colon cancer cells, and dissected the possible mechanisms underlying these effects. Crystal violet staining assay, flowcytometry assay, RT-PCR, Western blot, and luciferase reporter assay were used in our investigation.Firstly, we explored the effects of UA on proliferation, apoptosis, and cell cycle arrest in HCT116 colon cancer cells.Secondly,we test the effects of UA on TGF-β3 protein levels and the endogenous protein level of TGF-β3 in the available colon cancer cells and FHC cells.Lastly,we analysis the affect of UA on Wnt/β-catenin signaling. We used exogenous expression of TGF-β3 or TGF-β3 inhibitor,to study on the relationship between the proliferation inhibitory effect of UA in HCT116 cells and TGF-β3 and Wnt/β-catenin.We found that UA suppresses proliferation and induces apoptosis in HCT116 cells. UA markedly inhibits the expression of TGF-β3 concentration dependently in HCT116 cells,and it decreases the phosphorylation of Smad2/3. Exogenous expression of TGF-β3 partly reverses the anti-proliferation effect of UA in HCT116 cells. On the contrary, TGF-β3 inhibitor potentiates this anti-proliferation effect of UA in HCT116 cells.Mechanistically, we found that UA suppresses the activity of Wnt/β-catenin signaling in HCT116 cells through decreasing the level of β-catenin. Exogenous expression of TGF-β3 increases the level of β-catenin, and partly reverses the UA-induced decrease of β-catenin. However, TGF-β3 inhibitor potentiates the inhibitory effect of UA on β-catenin in HCT116 cells.