山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (5): 6-11.doi: 10.6040/j.issn.1671-7554.0.2015.648
刘相永,孙颖,黎莉
LIU Xiangyong, SUN Ying, LI Li
摘要： 目的 探讨多聚腺苷二磷酸核糖聚合酶-1(PARP-1)抑制剂对被沉默人类乳腺癌易感基因(BRCA1)的乳腺癌细胞株MCF-7及被沉默张力蛋白同源10号染色体丢失的磷酸酶基因(PTEN)的前列腺癌细胞株22RV1的作用。 方法 利用慢病毒介导的RNA干扰技术构建人乳腺癌MCF-7细胞的BRCA-1基因沉默细胞株及前列腺癌22RV1细胞的PTEN基因沉默细胞株。CCK-8法、流式细胞术分别检测PARP抑制剂AG014699对MCF-7、22RV1及转染细胞的增殖及周期分布的影响。Western blotting印迹法检测BRCA1、PTEN、DNA损伤修复酶RAD51、PARP、核因子κB(NF-κB)的蛋白表达。 结果 被沉默BRCA1基因的MCF-7细胞株及被沉默PTEN基因的22RV1细胞不表达RAD51。PARP抑制剂可明显抑制BRCA1基因沉默的MCF-7细胞及PTEN基因沉默的22RV1细胞的增殖,呈浓度时间依赖性,可能与RAD51、NF-κB表达降低有关;PARP抑制剂使细胞周期阻滞于G2/M期。 结论 PARP抑制剂能抑制存在DNA同源重组修复缺陷细胞(由BRCA1及PTEN功能异常所导致)的增殖,该作用可能与RAD51、NF-κB表达降低有关。
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