曲古抑素A对耐顺铂人肺腺癌细胞株凋亡影响及其机制的探讨  

Mechanism and effect of trichostatin A on apoptosis of cisplatin-resistant human lung adenocarcinoma cell line

作　　者：伍俊[1,2] 胡成平[1] 

机构地区：[1]中南大学湘雅医院呼吸内科,湖南长沙410008 [2]广东医学院呼吸疾病研究所,广东湛江524023

出　　处：《中华肿瘤防治杂志》2011年第13期1002-1005,1020,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:探讨曲古抑素A(TSA)诱导耐顺铂(DDP)人肺腺癌A549/DDP细胞株凋亡的作用及机制。方法:荧光染色检测细胞凋亡,蛋白质印迹法分析cFLIP、Caspase-8、Caspase-3和聚腺苷二磷酸核糖聚合酶(PARP)蛋白表达的变化,同时比色法测定Caspase-8活性。结果:曲古抑素A能诱导凋亡A549/DDP细胞株凋亡,随着浓度增加,其凋亡率逐渐增加。蛋白质印迹法结果显示,TSA处理细胞后,cFLIP蛋白水平下降,Pro-caspase-8减少,提示该酶被激活,促使Bid蛋白切割。Procaspase-3减少,提示酶被激活。PARP蛋白减少,切割的条带逐渐增加,提示PARP活性增加,促进细胞凋亡。比色法结果显示TSA对Caspase-8活性和cFLIP的影响具有浓度和时间依赖性。结论:TSA可以通过降低cFLIP水平激活Caspase-8诱导A549/DDP细胞凋亡。OBJECTIVE： To investigate the mechanism of Trichostatin A（TSA） induced apoptosis of cisplatin-resistant human lung adenocarcinoma cell line A549/DDP.METHODS： Morphologic assessment of apoptosis was performed with fluorescence microscope;Different proteins such as cFLIP,Caspase-8,Caspase-3,and PAPP were analyzed by Western blotting method,and Colorimetric method was used to measure Caspase-8 activities.REULTS： TSA induced apoptosis in cisplatin-resistant A549/DDP cells in dose-dependent manner,the apoptotic index（AI） was obviously higher.Treated by TSA,Western blotting analyses showed that the levels of cFLIP decreased,procaspase-8 decreased,and it resulted in the activation of Caspase-8 and Bid cleavage.The levels of procaspase-3 and PARP decreased,the cleavage of the activated PARP molecules would undergo more rapid apoptosis.Caspase-8 activity increased and cFLIP level decrease were regulated by TSA in a dose and time-dependent manner.CONCLUSION： TSA can induce A549/DDP cell apoptosis by decreasing cFLIP level and activating Caspase-8.

关 键 词：曲古抑素A A549/DDP CFLIP 细胞凋亡 Caspase-8 Bid 

分 类 号：R734.2[医药卫生—肿瘤]