人肺腺癌A549/DDP耐药细胞减弱顺铂诱导的细胞凋亡  

Cisplatin-induced apoptosis was reduced in cisplatin-resistant human lung adenocarcinoma cell line A549

作　　者：刘文哲 胡义德[2] 李金瀚[3] 许楚宏 陈娜娜[4] 

机构地区：[1]广州赤岗一七七中心医院肿瘤科,广东广州510317 [2]第三军医大学新桥医院全军呼吸研究所,重庆400037 [3]第一军医大学南方医院肿瘤科,广东广州510515 [4]第一军医大学药物研究所,广东广州510515

出　　处：《癌症》2000年第4期325-327,共3页Chinese Journal of Cancer

摘　　要：目的 :探讨人肺腺癌A5 49/DDP耐药细胞的多药抗药机理。方法 :应用形态学观察、琼脂糖凝胶电泳、原位DNA断裂点的末端标记法观察细胞凋亡的状况 ,用免疫组化法检测bcl 2基因的表达。结果 :癌细胞在顺铂作用下产生了典型的凋亡形态学改变。 3μg/ml、5 μg/ml、7μg/ml顺铂作用 48小时 ,A5 49细胞DNA裂解片断呈现典型的阶梯状排列条带 ;而在 5 μg/ml、7μg/ml顺铂作用 48小时 ,A5 49/DDP细胞才呈现相似的DNA条带。在 3μg/ml顺铂作用 12小时、18小时、2 4小时 ,A5 49/DDP的凋亡指数分别小于A5 49的凋亡指数。A5 49/DDPbcl 2基因的表达高于A5 49细胞。结论 :A5 49/DDP可抵抗顺铂诱导的细胞凋亡 ,这可能与其细胞bcl 2基因过度表达有关。bcl 2基因过度表达可能是A5 49/DDP细胞抗凋亡及抗药机理之一。Objective:To investigate multidrug resistant mechanisms in A549/DDP cell line Methods:Cell morphology, agarose gel electrophoresis and DNA 3 end labeling method were used to observe the apoptosis The bcl 2 protein was detected by immunohistochemical staining Results:Cells treated with 3 μg/ml cisplatin appeared typical morphological changes of apoptosis Nuclear DNA of A549 cells treated with cisplatin of 3 μg/ml,5 μg/ml or 7 μg/ml for 48 hours displayed ladder bands ,while nuclear DNA of A549/DDP cells treated with 5 μg/ml and 7 μg/ml cisplatin for 48 hours displayed ladder bands The apoptosis index of A549/DDP cells was lower than that of A549 cells at 12h, 18h and 24 h time points after exposing to 3 μg/ml cisplatin The expression of bcl 2 gene in A549/DDP cells was higher than that in A549 cells Conclusions:The A549/DDP cells undergo less apoptosis induced by cisplatin, which might be related to bcl 2 gene overexpression The overexpression of bcl 2 gene may be one of the important mechanisms, for reduced apoptosis and multidrug resistance in A549/DDP cells

关 键 词：多药抗药性 顺铂 细胞凋亡 肺腺癌 A549/DDP 

分 类 号：R734.2[医药卫生—肿瘤]