三氧化二砷诱导胃癌细胞凋亡及其对bcl-2基因和bax蛋白表达的影响

Effects of Arsenic Trioxide-Induced Apoptosis in Gastric Cancer Cells and Their bcl-2 Gene,bax Protein Expression

目的探讨三氧化二砷(As2O3)诱导胃癌细胞凋亡及其对bcl-2基因、bax蛋白表达的影响。方法分别以0μmol/L、1μmol/L、2μmol/L、4μmol/L和8μmol/L浓度的As2O3作用于胃癌SGC-7901细胞24 h、48 h和72 h,采用四甲基偶氮唑蓝(MTT)检测法检测各组吸光度值、细胞生长抑制率,采用流式细胞仪(FCM)检测bcl-2基因和bax蛋白的表达情况。结果随着As2O3浓度的增高及作用时间的延长,MTT吸光度值逐渐降低,1μmol/L、2μmol/L、4μmol/L、8μmol/L组分别与0μmol/L组比较,不同作用时间MTT吸光度值比较,差异均有统计学意义(P<0.05)。1μmol/L的As2O3对细胞增殖抑制作用较小,随着As2O3浓度的增高及作用时间的延长,细胞增殖抑制率相应增加,2μmol/L、4μmol/L、8μmol/L组分别与1μmol/L组比较,不同作用时间细胞增殖抑制率比较,差异均有统计学意义(P<0.05)。不同浓度的As2O3作用于SGC-7901细胞后,bcl-2基因呈低表达,bax蛋白呈高表达,bcl-2/bax比值降低且呈剂量依赖性,不同浓度As2O3组与对照组bcl-2基因、bax蛋白表达情况比较,差异均有统计学意义(P<0.05)。结论 As2O3对胃癌细胞的生长具有明显的抑制作用,其机制可能与下调bcl-2基因表达,上调bax蛋白表达从而诱导胃癌细胞的凋亡有关。

Objective To investigate the mechanism of arsenic trioxide-induced apoptosis in gastric cancer cells and their bcl-2 gene and bax protein expressions.Methods As2O3 with concentrations of 0 μmol/L,1 μmol/L,2 μmol/L,4 μmol/L and 8 μmol/L were used on gastric cancer SGC-7901 cells for 24 h,48 h and 72 h respectively.MTT assay was used to detect the absorbance value and cell growth inhibition rate,and flow cytometry（FCM）was used to detect bcl-2 gene and Bax protein expressions.Results MTT absorbance value decreased with the increase of the concentration of As2O3 and the increase of duration.The 1 μmol/L,2 μmol/L,4 μmol/L and 8 μmol/L groups were compared respectively with 0 μmol/L group,and the differences of absorbance value at different times were all statistically significant（P0.05）.As2O3 of 1 μmol/L concentration had little inhibitory effect on the proliferation of cells,but its inhibitory effect on cells proliferation increased with the increase of the concentration of As2O3 and the increase of duration.The 2 μmol/L,4 μmol/L and 8 μmol/L groups were compared with 1 μmol/L group respectively,and the differences of inhibitory rate of cells proliferation at different times were all statistically significant（P0.05）.The bcl-2 gene expression was low and the bax protein expression was high after the SGC-7901 cells were intervened by different concentrations of As2O3.bcl-2/bax ratio was decreased in a dose-dependent manner.The differences of bcl-2 gene expressions and bax protein expressions between groups with different As2O3 concentrations and the control group were statistically significant（P0.05）.Conclusion As2O3 has significant inhibitory effect on the growth of gastric cancer cells,and its mechanism may be related to the down regulate of bcl-2 gene expression and the up regulate of bax protein expression to induce the apoptosis of gastric cancer cells.