目的 观察PARP-1抑制剂Olaparib对非小细胞肺癌A549细胞凋亡的影响及可能机制.方法 常规培养A549细胞,分别给予不同剂量Olaparib(0、5、10、20、50μmol/L)和(或)SIRT1激动剂SRT1720(1μmol/L)、SIRT1抑制剂EX527(1μmol/L)处理24 h,MTT法检测细胞增殖,流式细胞术检测细胞凋亡,Western-blot检测细胞SIRT1及凋亡相关基因表达.结果 Olaparib处理A549细胞24 h后,细胞存活率、SIRT1及抗凋亡基因Bcl-2蛋白表达逐渐降低,凋亡率及促凋亡基因Bax、Caspase-3蛋白表达逐渐增加,呈剂量依赖性(P<0.05).单独给予EX527处理A549细胞能够模拟Olaparib的上述作用(P<0.05),但SRT1720和Olaparib联合组能够拮抗Olaparib的上述作用(P<0.05).结论 PARP-1抑制剂Olaparib通过下调SIRT1基因表达抑制A549细胞增殖,并诱导其凋亡.%Objective To investigate the effects of PARP inhibitor-Olaparib on the growth and apoptosis of non-small cell lung cancer A549 cells and its possible action mechanism .Methods The A549 cells were routinely cultured and treated with different doses of Olaparib (0、5,10,20,50μmol/L) and/or SRT1720(1μmol/L),EX527(1μmol/L)for 24h.Then MTT method was used to evaluate the proliferation of A 549 cells.Flow cytometer was used to analyze the apoptosis of A 549 cells, and Western Blot was performed to detect the expressions of SIRT 1 and apoptosis -related genes .Results After A549 cells were treated by different concentrations of Olaparib for 24h,the survival rate,the expression levels of SIRT1 and Bcl-2 of A549 cells were gradually decreased with the increase of Olaparib dosage ,meanwhile the apoptosis rate ,the expression levels of Bax and Caspase-3 of A549 cells were also gradually increased with the increase of Olaparib dosage ,with a dose-dependent manner (P<0.05).Moreover simple EX527 could simulate the effects of Olaparib on A549 cells (P <0.05),however, the SRT1720 combined with Olaparib could resist the effects of Olaparib as mentioned above .Conclusion PARP inhibitor-Olaparib can inhibit cell proliferation and induce apoptosis of A 549 cells by down-regulating the expression levels of SIRT 1 gene.
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