PARP-1在米托蒽醌诱导的MCF-7耐药细胞中的表达及作用分析  

Expression and function of PARP-1 in mitoxantrone-induced drug-resistance MCF-7 cells

作　　者：袁建辉[1] 周建孟[1] 姬娜娜[1] 吴德生[1] 徐新云[1] 刘建军[1] 柯跃斌[1] 程锦泉[1] 庄志雄[1] 

机构地区：[1]深圳市疾病预防控制中心深圳市现代毒理学重点实验室,广东深圳518020

出　　处：《癌变．畸变．突变》2010年第4期283-286,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(30500599;30571592);广东省自然科学基金(9151503102000019);广东省医学科研基金(A2009606)

摘　　要：目的:研究抗癌药物米托蒽醌诱导乳腺癌细胞系MCF-7耐药过程中,聚ADP-核糖聚合-1(poly ADP-ribosepolymerase-1,PARP-1)的表达变化,探讨MCF-7耐药细胞株中多药耐药的形成机制。方法:分别设米托蒽醌6个不同浓度实验组(0.005、0.01、0.02、0.04、0.08、0.16μmol/L),先以0.005μmol/L的米托蒽醌持续作用MCF-7细胞30d后,改用下一个剂量0.01μmol/L继续作用30d,依次按由低到高的浓度顺序进行,诱导产生耐药细胞。并设未用米托蒽醌处理的MCF-7为对照组。采用实时荧光定量RT-PCR和蛋白免疫印迹杂交分别检测米托蒽醌各浓度组细胞中PARP-1mRNA和蛋白的表达水平。结果:与对照组相比,随着米托蒽醌浓度的增加,PARP-1表达水平呈增高趋势,并且有剂量-反应效应,其中0.02、0.04和0.08μmol/L等3个浓度组的表达量显著高于对照组(P<0.05)。结论:米托蒽醌持续染毒可诱导MCF-7细胞中PARP-1的表达,其表达参与了肿瘤多药耐药的形成。OBJECTIVE：To study the expression and function of poly ADP-ribose polymerase-1（PARP-1）in mitoxantrone-induced drug-resisatance MCF-7 cells and analyse its drug-resistance mechanism.METHODS：MCF-7 cells were exposed to mitoxantrone in six concentration groups,0.005,0.01,0.02,0.04,0.08 and 0.16 μmol/L,for 30 days in turn with one blank control group.Both real-time quantitative RT-PCR and Western blot were used to measured PARP-1 expression.RESULTS：PARP-1 expression in MCF-7 cell was increased and displayed dose-effection relationship when exposed to higher concentrations of mitoxantrone,compared with the control group.There was a significant difference on PARP-1 expression when MCF-7 cells were exposed to mitoxantrone,0.02,0.04 and 0.08 μmol/L（P〈0.05）.CONCLUSION：PARP-1 expression was increased in MCF-7 cells after prolonged exposure to mitoxantrone and it could have participated in the formation of drug resistance in these cells.

关 键 词：米托蒽醌 聚ADP-核糖聚合酶-1 药物耐受 

分 类 号：R979.1[医药卫生—药品]