丹参酮ⅡA诱导人肺腺癌A549细胞凋亡  

Apoptosis inducing effect of Tanshinone ⅡA onhuman lung adenocarcinoma A549 cells

作　　者：戴支凯[1,2] 石京山[2] 吴芹[2] 余丽梅 徐庆[1] 

机构地区：[1]桂林医学院药理学教研室,广西桂林541004 [2]贵州省基础药理重点实验室,贵州遵义563003 [3]贵州省细胞工程重点实验室,贵州遵义563003

出　　处：《中国药理学通报》2010年第11期1505-1508,共4页Chinese Pharmacological Bulletin

摘　　要：目的探讨丹参酮ⅡA(TanshinoneⅡA,TanⅡA)抗人肺腺癌A549作用及其可能作用机制。方法通过细胞形态学和MTT法观察TanⅡA对A549细胞增殖的影响;应用Hoechest33258和PI双染法观察细胞凋亡;采用荧光分光光度计检测细胞内钙及线粒体膜电位;RT-PCR检测Bad和MT-1A mRNA的表达。结果 TanⅡA能抑制A549细胞增殖,且随TanⅡA剂量的增加和作用时间的延长而增强,TanⅡA作用A549细胞24、48和72h的IC50分别为117.85、14.87和6.89μmol·L-1。TanⅡA作用A549细胞24h后,A549细胞出现染色质聚集等典型的凋亡形态学改变,且随TanⅡA剂量的增加,A549细胞凋亡百分率逐渐增大。TanⅡA作用后,A549细胞的细胞内钙升高、线粒体膜电位降低、Bad mRNA表达增加、MT-1A mRNA表达下调。结论 TanⅡA具有抗A549作用,其诱导细胞凋亡可能与钙依赖性通路和MT-1A表达下调有关。Aim To investigate anticancer effect and potential mechanism of tanshinone Ⅱ A（Tan Ⅱ A） onhuman lung adenocarcinoma cell line A549 cells.Methods Antiproliferative effect of Tan ⅡA on A549 cells was evaluated by morphological examination and MTT assay.Apoptosis detection was carried out using Hoechest33258 and PI double-dyeing method.Intracellular Ca2＋ concentration and mitochondria membrane potential were detected by fluorospectrophotometer.Bad and MT-1A transcript analysis were carried by realtime reverse transcriptase-polymerase chain reaction （RT-PCR）.Results Tan ⅡA could inhibit proliferation of A549 cells in dose-and time-dependent manner.50% inhibiting concentration of Tan Ⅱ A on A549 cells in 24,48,and 72h was 117.85,14.87 and 6.89μmol·L-1 respectively.Typical apoptotic morphology such as chromatin aggregation was observed,and apoptotic inducing effect of Tan ⅡA on A549 cells for 24h was in a dose-dependent manner.After treated with Tan ⅡA,intracellular Ca2＋ concentration of A549 cells was increased,mitochondria membrane potential of the cells was decreased,relative Bad mRNA level of the cells was up-regulated and that of MT-1A was down-regulated.Conclusion Tan Ⅱ Ahas anticancer effect on A549 cells through apoptosis via calcineurin-dependent pathway and MT-1A downregulation.

关 键 词：丹参酮ⅡA 肿瘤 人肺腺癌A549细胞 细胞增殖 凋亡 钙依赖性通路 MT-1A 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]