GANT61诱导结肠腺癌细胞凋亡的作用及其机制

Effect of GANT61 on Apoptosis of Colon Adenocarcinoma Cells and Its Mechanism

目的探讨Gli抑制剂GANT61诱导人结肠腺癌细胞LOVO凋亡的机制。方法对Lovo细胞分别应用(0、10、20)μmol/L等不同浓度的GANT61处理24 h后,通过Western blot和流式细胞术观察处理结果,比较Gli1、Gli2、Fas和Bcl-2蛋白和细胞凋亡等相关蛋白的表达情况。结果GANT61可以显著下调LOVO细胞Gli1、Gli2和Bcl-2蛋白表达,增加Fas蛋白表达;Bcl-2蛋白表达显著低于DMSO组(P<0.01),Fas蛋白表达显著高于DMSO组(P<0.01);Caspase-3蛋白表达显著高于DMSO组(P<0.01)。结论GANT61诱导细胞凋亡,其作用机制可能与其通过特异性抑制LOVO细胞中Gli1、Gli2表达从而调节Fas、Bcl-2及Caspase-3蛋白表达有关。

Objective To investigate the mechanism of apoptosis induced by Gli inhibitor GANT61 in human colon adenocarcinoma Lovo cell.Methods Lovo cells were treated with different concentrations(0,10,20 mol/L)of GANT61 for 24 h.Western blot was used to observe the effects of GANT61 on Gli1,Gli2,Fas and Bcl-2 protein expression in Lovo cells.The expression of Gli1,Gli2 and CyclinD1 protein was observed by flow cytometry.Results GANT61 can significantly down-regulate the expression of Gli1,Gli2 and Bcl-2 proteins and increase the expression of Fas protein in Lovo cells.The protein expression of Bcl-2 was significantly lower than that in the DMSO group(P<0.01),the protein expression of Fas was significantly higher than that in the DMSO group(P<0.01).The protein expression of Caspase-3 was significantly higher than that in DMSO group(P<0.01).Conclusion GANT61 can induce apoptosis,and its mechanism may be related to the regulation of Fas,Bcl-2 and Caspase-3 protein expressions by specifically inhibiting the expressions of Gli1 and Gli2 in Lovo cells.