多聚二磷酸腺苷核糖聚合酶抑制剂对顺铂在肺癌治疗中增敏的作用研究

目的探讨多聚二磷酸腺苷核糖聚合酶(PARP-1)抑制剂4-氨基-1,8-萘二胺(4-AN)对顺铂在肺腺癌治疗中的增敏作用及相关机制。方法应用MTT法和克隆形成试验检测4-AN与顺铂联合作用对A549细胞的细胞毒性作用;应用单细胞凝胶电泳和微核试验检测4-AN与顺铂联合作用对A549细胞的遗传毒性作用。结果 4-AN可以增加顺铂对A549细胞的杀伤作用,且杀伤作用随4-AN浓度增加而增强;4-AN可以增加顺铂导致的DNA单双链断裂和染色体损伤,而且随药物浓度的增加,损伤作用增强。结论抑制PARP-1可以有效的增加A549对顺铂的敏感性,其作用机制可能是通过抑制A549细胞DNA单双链损伤修复,继而引起染色体损伤,导致细胞的生长和克隆受到抑制。

Effect of PARP-1 inhibitor on the sensitivity of cisplatin in treating A459 cells

Purpose To explore the effect of inhibition of poly(ADP-ribose) polymerase-1(PARP-1) on the sensitivity of cells to cisplatin in treating A549 cells.Methods A549 cells were treated with 4-amino-1,8-naphthalimide(4-AN) and DDP.The differences of cell viability were compared using MTT assay,and colony formation test.The genotoxicity between different groups was tested by comet assay and micronucleus test respectively.Results 4-AN exerted cytotoxicity of cisplatin in treating A549 cells in a dose-dependent manner.Moreover,4-AN exacerbated genotoxicity of cisplatin in treating A549 cells.Conclusion Inhibition of PARP-1 can significantly increase the sensitivity of A549 cells to cisplatin through inhibition of DNA damage repair.