癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (4): 283-286.doi: 10.3969/j.issn.1004-616x.2010.04.008

• 论著 • 上一篇    下一篇

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

袁建辉;周建孟;姬娜娜;吴德生;徐新云;刘建军;柯跃斌;程锦泉;庄志雄   

  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
  • 收稿日期:2010-03-25 修回日期:2010-04-26 出版日期:2010-07-30 发布日期:2010-07-30
  • 通讯作者: 庄志雄

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

YUAN Jian-hui;ZHOU Jian-meng;JI Na-na;WU De-sheng;XU Xin-yun;LIU Jian-jun;KE Yue-bin;CHENG Jin-quan;ZHUANG Zhi-xiong   

  1. Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518020, China
  • Received:2010-03-25 Revised:2010-04-26 Online:2010-07-30 Published:2010-07-30
  • Contact: ZHUANG Zhi-xiong

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-ribose polymerase-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、0.16 μmol/L),先以0.005 μmol/L的米托蒽醌持续作用MCF-7细胞30 d后,改用下一个剂量0.01 μmol/L继续作用30 d,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-1 mRNA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0.08 μmol/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。

关键词: 米托蒽醌, 聚ADP-核糖聚合酶-1, 药物耐受

Abstract: 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.

Key words: mitoxantrone, PARP-1, drug resistance

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