中文摘要：

目的：探讨多柔比星（doxorubicin）对乳腺癌MCF-7细胞表达DNA损伤修复相关蛋白乳腺癌易感蛋白1（breast cancer-associated protein 1,BRCA1）和多聚腺苷二磷酸核糖聚合酶-1[poly （ADP-ribose） polymerase-1,PARP-1]的影响。方法：蛋白质印迹法检测不同浓度的多柔比星干预并恢复不同时间后,MCF-7细胞表达BRCA1和PARP-1的水平及其PARP-1活性的动态变化。FCM法检测多柔比星和PARP-1抑制剂3-氨基苯酰胺（3-aminobenzamide,3-ABA）单独或联合干预后MCF-7细胞及SKBR3.0细胞（BRCA1突变型乳腺癌细胞）的凋亡情况。结果：随着多柔比星浓度的提高,PARP-1的活性产物聚腺苷二磷酸核糖[poly（ADP-ribose）,PAR]逐渐增加（P〈0.01）,然而其全长表达（相对分子质量为1.13×105的片段）略有降低,断裂（相对分子质量为8.9×104的片段）有所增加;而BRCA1表达却呈现先增加后减少的趋势（P〈0.01）。PARP-1活性随着恢复时间的延长逐渐升高（P〈0.01）,但全长PARP-1表达变化不大,断裂略有减弱;BRCA1表达却逐渐减少（P〈0.01）。3-ABA能抑制PARP-1活性（P〈0.01）,诱导PARP-1断裂,但不影响BRCA1表达。多柔比星及3-ABA都能诱导MCF-7细胞凋亡,与对照组相比较,其差异均有统计学意义（P〈0.05）;多柔比星和3-ABA两者联合作用时能进一步增加BRCA1野生型乳腺癌细胞MCF-7的凋亡,与多柔比星及3-ABA单独使用相比较,差异具有统计学意义（P〈0.05）;多柔比星和3-ABA两者联合作用时能诱导BRCA1突变型乳腺癌细胞SKBR3.0发生凋亡,与两者联合作用MCF-7细胞的影响相比较,差异具有统计学意义（P〈0.05）。结论：多柔比星干预能影响DNA损伤修复蛋白PARP-1的活性及BRCA1的表达。多柔比星和PARP-1抑制剂3-ABA都能诱导MCF-7细胞凋亡,两者联合应用能增加这种凋亡诱导效应。

英文摘要：

Objective： To investigate the effects of doxorubicin on the expressions of DNA-damage/ repair-related proteins BRCA1 （breast cancer-associated protein 1）and PARP-1 [poly（ADP-ribose） polymerase-1] in BRCA1 wild-type breast cancer MCF-7 cells. Methods： The MCF-7 cells were treated with doxorubicin, then the expressions of BRCA1 and PARP-1 and the activity of PARP-1 in the cells recovering after different time peroids were detected by Western blotting. The apoptotic rates of MCF-7 cells and SKBR3.0 cells （BRCA1 mutant-type breast cancer cells） after intervention with doxorubicin and PARP-1 inhibitor 3-ABA （3-aminobenzamide） were detected by FCM （flow cytometry）. Results： After MCF-7 cells were treated with different concentrations of doxorubicin for 24 h and then recovered for 12 h, the expression of PAR [poly（ADP-ribose）], an active product of PARP-1, was increased in a dose-dependent manner （P 〈 0.01）, but the expression of full-length PARP-1 （the molecular mass is 1.13-10s） was in aslightly decrease accompanied by more cleavage fragments of PARP-1 （the molecular mass is 8.9）〈104）, while the expression of BRCA1 was firstly increased and then decreased （P 〈 0.01）. After MCF-7 cells were treated with 1 IJmol/L doxorubicin for 24 h and then recovered for different time peroids, the activity of PARP-1 （PAR） was increased gradually over time peroid of recovery （P 〈 0.01）, but the expression of full- length PARP-1 had no significant change with less cleavage fragments of PARP-1, while the expression of BRCA1 was decreased gradually （P 〈 0.01）. The activity of PARP-1 was significantly inhibited by 3-ABA （P 〈 0.01） via inducing its cleavage, which didn＇t affect BRCA1 expression （P 〉 0.05）. Both doxorubicin and 3-ABA alone could significantly induce the apoptosis of MCF-7 cells （P 〈 0.05）, and the combination of the two could further increase the apoptosis of BRCA1 wild-type breast MCF-7 cells （P 〈 0.05）. Doxorubicin in combinat