PARP抑制剂对顺铂抑制肺癌细胞增殖影响的研究  

Effect of PARP inhibitors on the proliferation inhibition by cisplatin in lung cancer cell lines

作　　者：刘俊玲[1] 孙蕊[2] 李万湖[3] 王宇[1] 蔡修宇[1] 姜文奇[1] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学附属肿瘤防治中心内科,广东广州510060 [2]华南肿瘤学国家重点实验室中山大学附属肿瘤防治中心鼻咽科,广东广州510060 [3]山东省肿瘤防治研究院磁共振室,山东济南250117

出　　处：《中华肿瘤防治杂志》2012年第17期1290-1293,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：广东省医学科学技术研究基金(A2011199;A2010188);中山大学肿瘤防治中心出国留学人员科研启动基金(303041217001)

摘　　要：目的:以顺铂(DDP)敏感和耐药肺癌细胞系为实验对象,探讨聚腺苷二磷酸核糖聚合酶〔Poly(ADP-ribose)polymerase,PARP〕抑制剂对DDP抑制肺癌细胞增殖作用的影响。方法:MTT法检测DDP、PARP抑制剂单药及其两者联合对DDP敏感和耐药肺癌细胞系增殖的抑制作用。应用蛋白免疫印迹方法,检测肺癌细胞系中PARP-1和PARP-2的表达,以及DDP激活PARP生成聚腺苷二磷酸核糖〔Poly(ADP-ribose),PAR〕与PARP抑制剂对PARP的抑制作用。结果:蛋白质印迹法结果显示PARP-1在PC9、PC14、SBC3亲代DDP敏感肺癌细胞系及其子代DDP耐药细胞系之间的表达差异有统计学意义,P值分别为0.028、0.013和0.008。DDP作用于肺癌细胞系激活PARP生成PAR在40min达到高峰,但在60min即迅速降低,且DPQ可抑制PAR的生成。而MTT结果显示,DPQ联合DDP抑制肺癌敏感和耐药细胞系的抗增殖作用与DDP单药作用比较差异均无统计学意义(P>0.05,t<0),表明DPQ没有增效DDP的作用。结论:在敏感和耐药肺癌细胞系中,PARP抑制剂与DDP联合无明显的协同增效作用,提示PARP-1表达差异与肺癌细胞对DDP敏感或者耐药无关,说明尚需进一步探讨PARP抑制剂与DNA损伤药物联合使用对肺癌的影响。OBJECTIVE： To observe the effect of poly （ADP-ribose） polymerase（PARP） inhibitors on the growth inhibition by cisplatin in the Cis-sensitive and Cis-resistant lung cancer cell lines. METHODS： The effect of proliferation inhibition of the combination of PARP inhibitors with cispaltin and that of the single drugs were detected by MTT assay. The difference of expression of PARP-1 and PARP-2 between the Cis-sensitive and Cis-resistant cell lines, together with the formation of Poly（ADP-ribose） （PAR） following the exposure of cisplatin and the inhibition of PAR by PARP inhibi- tots were analyzed by western blot analysis. RESULTS： The expression of PARP-1 between the parent cisplatin sensitive cell lines Pcg, PC14, SBC3 and their sub cisplatin resistant cell lines was significantly different（P=0. 028,0. 013, 0. 008）. After exposure of 60 minutes to eisplatin, PARP was activated rapidly and the formation of PAR was the highest at 40 minutes and could be inhibited by DPQ in the lung cancer cell lines（P^0.05 ,t^C0）. PARP inhibitors did not poten- tiate the effect of growth inhibition of cisplatin in all lung cancer cell lines. CONCLUSIONS： PARP inhibitors brings effects of no potentiation of growth inhibition of cisplatin in all the Cis-sensitive and Cis-resistant lung cancer cell lines, which suggests that the different expression of PARP-1 is not related with cell lines whether sensitive to eisplatin or not. Further investigations are still needed to observe the effect of PARP inhibitors on proliferation inhibition by other DNA damage chemotherapy agents in lung cancer cell lines.

关 键 词：肺肿瘤 聚ADP核糖聚合酶类 顺铂 细胞培养 

分 类 号：R734.2[医药卫生—肿瘤]