三氧化二砷对膀胱癌细胞BIU-87耐药相关基因的影响

目的:探讨三氧化二砷(arsenic trioxide,As2O3)对耐羟基喜树碱的膀胱癌细胞株BIU-87/HCPT耐药性逆转的机制.方法:用As2O3与羟基喜树碱联合处理BIU-87/HCPT细胞后,用四甲基偶氮唑蓝法(MTT)检测细胞增殖,流式细胞仪检测细胞周期、细胞凋亡、P-gp、MRP1、GST-π和生存素(survivin)表达的变化.结果:As2O3与羟基喜树碱联合处理耐药膀胱移行细胞癌株BIU-87/HCPT 细胞后,细胞生长受到明显抑制.单独应用As2O3的凋亡率为11.07%,As2O3联合羟基喜树碱后的凋亡率为18.23%,凋亡细胞百分比较对照组明显增多,As2O3明显增加羟基喜树碱的作用(P<0.05).As2O3使P-gp、MRP 1、GST-π和survivin的表达明显减少,且均具有浓度依赖性(P<0.05).结论:As2O3可减少耐药相关基因的表达,部分逆转膀胱癌细胞的耐药性,促进凋亡,且呈现浓度依赖性.

Effect of As2O3 on multidrug resistance gene in bladder cancer cell

Objective:To investigate the mechanism of As2O3 on reversing multidrug resistance in BIU-87/HCPT bladder cancer cell line.Methods: To treat the BIU-87/HCPT cells by Hydroxycamptothecin and As2O3 at different concentration,then detect the proliferation activity of BIU-87/HCPT by MTT assay.Expression of P-gp,MRP1,GST-π,survivin,cell cycle and apoptosis were detected by flow cytometry.Results: Treated by As2O3 and Hydroxycamptothecin,the proliferation activity of BIU-87/HCPT cells were significantly slowed down compare to the control group,with an evident time and dose-response relationship.As2O3 can induce the apoptosis of BIU-87/HCPT cells with concentration dependent.The apoptosis rate of BIU-87/HCPT cell was 11.07% in As2O3 group and 18.23% in As2O3 combined with chemotherapy(P<0.05),As2O3 significantly enhanced the effect of chemotherapy.After cultured with As2O3 the expression of P-gp,MRP 1,GST-π,survivin was downregulated significantly with concentration dependent(P<0.05).Conclusion: As2O3 can downregulate the expression of multidrug resistance gene,and partially reverse the multidrug resistance and induce the apoptosis of BIU-87/HCPT cell with concentration dependant.