Effect of FXR agoniston GW4064 on the proliferation of colorectal cancer cells

OBJECTIVE:To determine the influence mechanism of farnesoid X receptor(FXR) agoniston GW4064 on proliferation of colorectal cancer cells.METHODS:After HT29 cells were treated with FXR agonist GW4064(0.01,0.1 and 1 μmol/L),the change of HT29 proliferation were detected by MTT.The change of FXR,IBABP and Cyclin D1 expression were determined by the real-time quantitative PCR and Western Blot.RESULST:GW4064 inhibited HT29 proliferation,and when concentration was 0.1-1 μmol/L,GW4064 was in a dose dependent manner(0.1 μmol/L group compared with the control group,t=4.370,P0.05;0.1 μmol/L group compared with 1 μmol/L group,t=8.325,P0.01).GW4064 did not enhance FXR expression of HT29(1 μmol/L group compared with the control group,t=0.392,P0.05),but increased the expression of IBABP,and was in a dose(0.1-1 μmol/L) dependent manner(0.1 μmol/L group compared with the control group,t=13.043,P0.01;0.1 μmol/L group compared with 1 μmol/L group:t=9.001,P0.01).GW4064 reduced the expression of Cyclin D1,and was also in a dose(0.1-1 μmol/L) dependent manner(0.1 μmol/L group compared with the control group,t=4.387,P0.05;0.1 μmol/L group compared with 1 μmol/L group,t=2.790,P0.05).CONCLUSION:GW4064 may inhibit HT29 proliferation by enhancing FXR activity and reducing expression of Cyclin D1,which suggests that FXR ligand may be beneficial for colorectal cancer.