Effect Of DCA Combined With TGR-5 On Metastasis Of Cholangiocarcinoma Cells

Background: Cholangiocarcinoma is a malignant tumor with poor differentiation and high invasiveness.The incidence of cholangiocarcinoma is low,but in recent years,the incidence of cholangiocarcinoma has increased significantly in the world.Bile acids are an important part of bile and have received much attention in recent years.Deoxycholic acid(DCA)is a type of free bile acid that is involved in the development of cholangiocarcinoma.As a ligand,bile acids are capable of activating a variety of receptors,including G protein-coupled bile acid receptor 5(TGR-5).Studies have shown that TGR-5 can be activated by a variety of bile acids,and TGR-5 can also play a role in the development of various tumors by activating various signaling pathways.The role and mechanism of angiogenesis in cholangiocarcinoma is still unclear.Objective To investigate the role of bile acid(DCA)and bile acid receptor TGR-5 in the proliferation and metastasis of cholangiocarcinoma cells.Methods The expression of TGR-5 in cholangiocarcinoma cells RBE and normal bile duct cells was detected by PCR and Western blot.The effect of different concentrations of DCA on the proliferation of RBE cells was detected by MTT.The effect of DCA on the invasiveness of RBE cells was detected by Transwell.The expression levels of EMT-related proteins(E-cadherin,N-cadherin,Vimentin and Snail)in RBE cells were detected by Western blot.Results TGR-5 mRNA and protein are highly expressed in cholangiocarcinoma cell line RBE and low level in normal bile duct cells.The activity of DCA can increase the activity of cholangiocarcinoma cells and is positively correlated with DCA concentration.Transwell results show that DCA is compared with control group.The number of RBE cells in the group increased significantly.The results of Western blots showed that the expression of E-cadherin was down-regulated in RBE cells of DCA group,while the expression of N-cadherin,Vimentin and Snail was up-regulated,and EMT was induced in RBE cells.Conclusion TGR-5 is highly expressed in cholangiocarcinoma RBE cells and is closely related to the progression of cholangiocarcinoma.DCA can enhance the viability of RBE cells and promote their proliferation.DCA can up-regulate the expression of Snail,N-cadherin and Vimentin,down-regulate the expression of E-cadherin,induce EMT in RBE cells,and promote the metastasis of cholangiocarcinoma cells.