FXR配体GW4064对大肠癌细胞增殖影响机制的探讨

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

目的:探讨法尼酯衍生物X受体(FXR)配体GW4064对大肠癌细胞增殖影响的机制。方法:运用GW4064(0.01、0.1和1μmol/L)作用HT29后,应用MTT法检测HT29增殖的变化,应用实时荧光定量PCR法和蛋白质印迹法检测FXR、IBABP及Cyclin D1表达的变化。结果:GW4064能抑制HT29增殖,浓度在0.1～1μmol/L有浓度依赖性。0.1μmol/L作用组与对照组比较,t=4.370,P<0.05;0.1μmol/L作用组与1μmol/L作用组比较,t=8.325,P<0.01。GW4064没有增强HT29FXR的表达,1μmol/L组与对照组比较,t=0.392,P>0.05,但能增加IBABP表达,且GW4064浓度在0.1～1μmol/L有浓度依赖性。0.1μmol/L作用组与对照组比较,t=13.043,P<0.01;0.1μmol/L作用组与1μmol/L作用组比较,t=9.001,P<0.01。GW4064能减少Cyclin D1表达,且浓度在0.1～1μmol/L也有浓度依赖性。0.1μmol/L作用组与对照组比较,t=4.387,P<0.05;0.1μmol/L作用组与1μmol/L作用组比较,t=2.790,P<0.05)。结论:GW4064可能通过增强FXR活性,减少Cyclin D1表达来抑制HT29增殖,为FXR配体治疗大肠癌提供实验依据。

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 umol/L）,the change of HT29 proliferation were detected by MTT. The change of FXR,IBABP and Cyclin D1 ex- pression were determined by the real-time quantitative PCR and Western Blot. RESULST：GW4064 inhibited HT29 prolif- eration,and when concentration was 0.1--1 umol/L,GW4064 was in a dose dependent manner （0.1 umol/L group com- pared with the control group, t = 4. 370, P〈 0. 05 ; 0. 1 ~mol/L group compared with 1 bLmol/L group, t = 8. 325, P〈 0.01）. GW4064 did not enhance FXR expression of HT29 （1 umol/L group compared with the control group,t=0. 392, P〉0.05） ,but increased the expression of IBABP, and was in a dose （0.1-1umol/L） dependent manner （0.1 umol/L group compared with the control group, t= 13. 043, P〈0. 01 ; 0.1 tLmol/L group compared with 1 umol/L group： t ： 9. 001 ,P（0.01）. GW4064 reduced the expression of Cyclin D1 ,and was also in a dose （0.1-1 umol/L） dependent man- ner （0.1/umol/L group compared with the control group, t=4. 387, P（0.05;0.1 umol/L group compared with 1/umol/L group,t = 2. 790,P（0.05）. CONCLUSION： GW4064 may inhibit HT29 proliferation by enhancing FXR activity and re- ducing expression of Cyclin Dl,which suggests that FXR ligand may be beneficial for colorectal cancer.