XAV939对肝癌细胞增殖及糖酵解的影响

摘要

目的：探讨 Wnt／β－catenin 信号通路特异性抑制剂 XAV939对肝癌细胞增殖及糖酵解过程的影响。方法：MTT 方法检测不同浓度 XAV939对肝癌细胞 Bel －7402、HCCLM3增殖能力的影响；Western blot 方法检测 XAV939对肝癌 Bel －7402、HCCLM3细胞 Wnt／β－catenin 信号通路关键基因和其下游靶基因表达的影响，以及对糖酵解过程中关键调控基因表达的影响。运用 SPSS 19．0统计软件分析各组间的差异。结果：MTT 结果表明不同浓度的 XAV939能够不同程度的抑制 Bel －7402、HCCLM3细胞增殖能力，XAV939对两种细胞的抑制率接近50％时，浓度分别为：30μmol／L、20μmol／L。Western blot 结果显示，XAV939可以显著抑制 Wnt／β－catenin 及其下游基因 c －myc、Cyclin D1的表达，有效抑制β－catenin 信号通路活性；同时，XAV939可以通过抑制 HK －2、LDHA 而非 Glut －1的蛋白表达水平来抑制肝癌细胞的糖酵解过程。结论：XAV939在体外能够有效抑制肝癌细胞 Wnt／β－catenin 信号通路及其依赖性细胞增殖和糖酵解过程。%Objective:To investigate the effect of XAV939 on proliferation and glycolysis of hepatocellcular carci-noma cell lines.Methods:Methyl thiazol tetrazolium (MTT)analysis was performed to detect the inhibition of XAV939 on cell proliferation in Bel -7402 and HCCLM3 cells.Inhibitory effect of XAV939 on the expression of Wnt/β-catenin signaling pathway protein and genes involved in glycolysis was tested by western blot analysis.SPSS 19.0 was used for statistical analysis.Results:MTT assay showed that different concentrations of XAV939 exhibit dif-ferent degree of suppressive effects on Bel -7402 and HCCLM3 cells proliferation,and the inhibition rate was about 50% when Bel -7402 and HCCLM3 were respectively treated with 30μmol/L and 20μmol/L inhibitor.Western blot analysis indicated that XAV939 showed an effective inhibition on Wnt/β-catenin signaling pathway,with β-cate-nin,c -myc and Cyclin D1 down -regulated,meanwile,XAV939 could repress the process of glycolysis of Bel -7402 and HCCLM3 cells by repressing the expression of HK -2,LDHA but not Glut -1.Conclusion:XAV939 exhibited an effectively inhibition of Wnt/β-catenin signaling pathway,cell proliferation and the process of the glycolysis de-pented on Wnt/β-catenin pathway.