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机构地区:[1]山东大学附属省立医院妇产科,济南250021 [2]山东大学附属省立医院中心实验室,济南250021
出 处:《山东大学学报(医学版)》2012年第1期46-50,共5页Journal of Shandong University:Health Sciences
基 金:山东省自然基金资助项目(ZR2009CM104);山东省医药卫生科技发展计划项目(2009HZ065)
摘 要:目的探讨聚腺苷酸二磷酸核糖聚合酶-1[Poly(ADP-ribose)polymerase-1,PARP-1]抑制剂PJ34对卵巢癌耐药细胞株C13*细胞生长活性及耐药性的影响。方法应用四甲基偶氮唑蓝(MTT)及流式细胞术检测PJ34对C13*细胞顺铂敏感性、凋亡和周期的影响;免疫荧光及蛋白印迹法(Western blot)检测PJ34处理前后PARP-1的表达情况。结果 C13*细胞增殖抑制率及对顺铂的敏感性随顺铂及PJ34浓度的增加而增强(P<0.05);细胞凋亡率随PJ34浓度的增加而增高(P<0.05);周期为PJ34浓度越高,G0/G1期细胞越多,S期细胞越少;PJ34可下调细胞中PARP-1的表达,顺铂与PJ34合用后,PARP-1蛋白表达量明显降低(P<0.01)。结论 PJ34能显著下调C13*细胞内PARP-1表达,抑制细胞增殖,促进细胞凋亡,增加细胞对顺铂的敏感性,有效逆转C13*细胞对顺铂的耐药性。Objective To investigate the effects of poly(ADP-ribose)polymerase-1(PARP-1) inhibitor PJ34 on the growth activity and cisplatin resistance of cisplatin-resistant ovarian cancer C13* cells in vitro.Methods MTT assay and flow cytometry were used to determine influences of PJ34 on cisplatin sensitivity,apoptosis and the cell cycle of C13* cells.The expression level of PARP-1 in C13* cells was determined using immunofluorescence microscopy and Western blot,and changes induced by PJ34 treatment were investigated.Results The inhibitory ratio and cisplatin sensitivity of C13* cells were significantly increased with increases of concentrations of platinum(Pt) and PJ34(P0.05).The apoptosis ratio of C13* cells was significantly increased with the increase of the concentration of PJ34(P0.05).The proportion of cells in the G0/Gl phase in the high concentration PJ34-treated group was larger than that in the low concentration PJ34-treated group.PJ34 down-regulated the PARP-1 expression in C13* cells,which was remarkably decreased when Pt and PJ34 co-treated(P0.01).Conclusion PJ34 remarkably down-regulates the PARP-1 protein expression,inhibits proliferation activity,promotes apoptosis,and increases sensitivity to cisplatin of C13* cells.Hopefully,PJ34 could effectively reverse resistance of C13*cells to cisplatin.
关 键 词:聚腺苷二磷酸核糖聚合酶-1 PJ34 卵巢癌 耐药性
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