苦参碱联合奥沙利铂对人结肠癌SW620细胞增殖、凋亡及p53蛋白表达的影响

Effect of matrine plus oxaliplatin on proliferation,apoptosis and p53 expression of human colon cancer cell line SW620

目的探讨苦参碱(Ma)联合奥沙利铂(OXA)对人结肠癌SW620细胞增殖、凋亡、细胞周期分布及p53蛋白表达的影响。方法用不同浓度的Ma,OXA和两药联用分别处理人结肠癌细胞SW620,采用四甲基偶氮唑盐(MTT)比色法测定药物对细胞的增殖抑制率,流式细胞术检测用药后细胞周期分布和细胞凋亡率,蛋白质免疫印迹(Western blot)检测p53蛋白的表达情况。结果 Ma,OXA单用和联用均能抑制SW620增殖(P<0.05),呈时间-浓度依赖性,且两药联用对人结肠癌细胞SW620的增殖抑制率明显高于单用(P<0.05);OXA可在一定程度上诱导细胞凋亡(P<0.05),与Ma联用后,诱导细胞凋亡作用明显增强(P<0.05);OXA能够使细胞阻滞于G2/M期(P<0.05),联用Ma对G2/M期的阻滞作用更加明显(P<0.01);OXA作用SW620细胞后p53蛋白表达增强(P<0.05),联合Ma作用SW620细胞后p53蛋白表达上调较单用明显增强(P<0.05)。结论 Ma和OXA均可抑制人结肠癌SW620细胞的增殖,诱导细胞的凋亡,二者联合应用具有协同作用,可提高OXA化疗的敏感性,该作用可能与提高细胞内p53蛋白的表达有关。

Objective To investigate the effect of matrine（Ma）plus oxaliplatin（OXA）on the proliferation,apoptosis and p53 expression of human colon cancer cell line SW620.Methods The SW620 cells were treated with different concentrations of Ma alone,OXA alone and Ma plus OXA.The proliferation inhibitory rate was evaluated by MTT assay,the cell cycle and cell apoptosis rate were determined by flow cytometry analysis,and the p53 expression level was measured by Western blot.Results Ma alone,OXA alone and Ma plus OXA could inhibit the proliferation of SW620 cells in a time-and dose-dependent manner（P0.05）.The inhibitory effect of Ma plus OXA on SW620 cells was significantly greater than that of Ma alone or OXA alone（P0.05）.Besides,OXA could induce cell apoptosis（P0.05）,and this effect was significantly enhanced when combined with Ma（P0.05）;OXA could also induce SW620 cells to be arrested at G2/M phase（P0.05）,and this blocking effect became more obvious after the addition of Ma（P0.01）;OXA could increase the p53 expression level（P0.05）and such an effect was significantly magnified when OXA was used in combination with Ma（P0.05）.Conclusion Both Ma and OXA can inhibit the proliferation and induce the apoptosis of human colon cancer cell line SW620.The combination of Ma and OXA has a synergistic effect and could increase the sensitivity of OXA chemotherapy,which may be related to the enhanced expression of p53.