浙江医学Issue(13):1124-1128,5.
藤黄酸诱导肺癌细胞H1975凋亡的机制研究
Gambogic acid induces apoptosis of lung cancer H1975 cells by activating JNK signaling pathway and upregulating ROS
摘要
Abstract
Objective To investigate the effect of gambogic acid (GA) on apoptosis of human lung cancer H1975 cel s and its mechanisms. and JNK signaling pathway in kil ing lung cancer cells by GA. Methods Human lung cancer H1975 cel s were treated with GA (1, 2.5 and 5μmol/L). Cel proliferation was analyzed by MTT assay;cel apoptosis was detect-ed by Annexin V- FITC/PI double staining. The Reactive oxygen species (ROS) was measured by DCFH- DA method; the changes of mitochondrial membrane potential (MMP) were detected by JC- 1 probe method; the activation of JNK signaling pathway and the expression of mitochondrial apoptosis- related proteins were detected by Western blot. Results Compared with control group, the proliferation of H1975 cel s was inhibited by GA in a dose- dependent manner (P<0.05 or 0.01): the apoptotic rates were increased by 25.2%, 51.8%and 75.1%, after cells were treated with 1, 2.5 and 5μmol/L of GA for 24h. The expression of cleaved caspase- 9, cleaved caspase- 3 and cleaved PARP in GA group were significantly higher than those in control group in a dose- dependent manner (P<0.05 or 0.01). Compared with control group, the ROS levels were significantly increased and the expression of phospho- JNK(p- JNK) was up- regulated after treated with GA for 2h. After treated by GA for 16 h, the MMP in GA group was decreased significantly compared with the control group(P<0.05). GA increased the expres-sion of pro- apoptotic protein Bax, Bak, Bik and decreased the expression of pro- survival protein Bcl- 2 (P<0.05 or 0.01). Conclusion Gambogic acid can induce the apoptosis of human lung cancer H1975 cel s through up- regulating the intracel ular level of ROS to activate JNK signaling pathway, the latter triggers loss of MMP and activation of mitochondria apoptosis path-ways.关键词
藤黄酸/肺癌H1975细胞/活性氧自由基/JNK信号通路/凋亡Key words
Gambogic acid/Lung cancer H1975 cel/Reactive oxygen species/JNK signaling pathway/Apoptosis引用本文复制引用
何蕾,王宝辉,吕望,泮辉,胡坚..藤黄酸诱导肺癌细胞H1975凋亡的机制研究[J].浙江医学,2015,(13):1124-1128,5.基金项目
浙江中医药大学校级课题 ()