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藤黄酸诱导肺癌细胞H1975凋亡的机制研究

何蕾 王宝辉 吕望 泮辉 胡坚

浙江医学Issue(13):1124-1128,5.
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

何蕾 1王宝辉 2吕望 3泮辉 1胡坚1

作者信息

  • 1. 310003 杭州,浙江大学附属第一医院心胸外科
  • 2. 浙江国际旅行卫生保健中心工作
  • 3. 浙江中医药大学附属第一医院中心实验室
  • 折叠

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 ()

浙江医学

OACSTPCD

1006-2785

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