PJ34对肺腺癌顺铂耐药细胞增殖及耐药性的影响  

Study of reversal effect of PARP-1 inhibitor PJ34 on cisplatin-resistance in human lung adenocarcinoma cells

作　　者：姚圆圆[1] 郝吉庆[1] 

机构地区：[1]安徽医科大学第一附属医院肿瘤内科,安徽合肥230022

出　　处：《中国药理学通报》2015年第6期865-870,共6页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金计划项目(No 1308085MH142);安徽省对外科技合作计划项目(No 1503062023)

摘　　要：目的探讨第3代选择性PARP-1抑制剂PJ34对肺腺癌顺铂耐药细胞株A549/DDP生长活性及耐药性的影响。方法使用不同浓度梯度的顺铂(DDP)、PJ34单药或联合作用于A549/DDP细胞,MTT法检测各药物对细胞的增殖抑制率;流式细胞术检测细胞凋亡率;Western blot检测细胞内PARP-1蛋白、MDR相关蛋白(LRP、GST-π)的表达水平。结果PJ34单药对A549/DDP细胞有明显的抑制作用,无毒剂量的PJ34可明显增强A549/DDP细胞对顺铂的敏感性,诱导细胞凋亡,使细胞内PARP-1蛋白、MDR相关蛋白(LRP、GST-π)的表达水平明显降低。结论 A549/DDP细胞的顺铂耐药性与细胞内PARP-1蛋白的过度表达有关,PJ34有明显的顺铂增敏作用,能部分逆转A549/DDP细胞对顺铂的耐药性,其机制可能与诱导细胞凋亡,降低细胞内LRP、GST-π的蛋白表达水平有关。Aim To investigate the reversal effect of PARP-1 inhibitor PJ34 on cisplatin-resistance in hu-man lung adenocarcinoma A549/DDP cells and the mechanism. Methods A549/DDP cells were treated with PJ34 alone or combined with cisplatin. The effects of proliferation inhibition were assayed by MTT method. The apoptosis ratios of cells were analyzed by flow cytometry. The protein expression of PARP-1 and LRP, GST-π were measured by Western blot assay. Results PJ34 could inhibit the proliferation of A549/DDP cells alone. The non-toxic dose of PJ34 could signifi-cantly resensitize A 5 4 9/ DDP cells to cisplatin , induce apoptotic,lower the expression of PARP-1 and resist-ance-associated protein LRP and GST-π. Conclusion PJ34 could inhibit the proliferation of A549/DDP cells and resensitize A549/DDP cells,partially reverse cisplatin-resistance in A549/DDP cells, with a probable mechanism relating to increased apoptotic rate,and lowered expression of PARP-1 and resistance-associat-ed protein LRP and GST-π.

关 键 词：肺腺癌 聚腺苷二磷酸核糖聚合酶-1抑制剂 顺铂 耐药性 凋亡 机制 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R730.53[医药卫生—基础医学]