Li Rui, Chen Yan, Zhao Fei, Liu Yuan, Wen Lu, Zeng Ling-lan
Department of Hematology, Huazhong Science and Technology University, Wuhan 430022, China.
Zhonghua Zhong Liu Za Zhi. 2009 Nov;31(11):810-4.
To investigate the effects of gambogic acid (GA) on the proliferation inhibition and apoptosis induction in Human lung adenocarcinoma A549 cells in vitro, as well as the regulation of steroid receptor coactivator-3 (SRC-3) to explore the relationship between them.
The effect of GA on the growth of A549 cells was studied by MTT assay. Apoptosis was detected by Hoechst 33258 staining. The localization of SRC-3 was determined by confocal laser scanning microscopy. Western blot and RT-PCR technique were applied to assess the expression of SRC-3.
GA presented a striking proliferation inhibition potency on A549 cells in vitro, as well as apoptosis induction activity in a time- and dose-dependent manner. The IC(50) value for 24 h was (3.17 +/- 0.13) micromol/L. Overexpression of SRC-3 was found in A549 cells, whereas the SRC-3 protein and mRNA expression levels were significantly downregulated in A549 cells induced by GA in a dose-dependent manner. The location of SRC-3 was situated mainly in the cell nuclei.
GA exhibits a potent proliferation inhibition and apoptosis induction in human lung adenocarcinoma A549 cells, which might correspond to the downregulation of the expression of SRC-3. Thus, it promises to be a new target drug for lung cancer treatment.
探讨藤黄酸（GA）对人肺腺癌A549细胞体外增殖抑制和凋亡诱导的作用，以及对类固醇受体辅激活因子-3（SRC-3）的调控，以探索它们之间的关系。
采用MTT法研究GA对A549细胞生长的影响。通过Hoechst 33258染色检测细胞凋亡。利用共聚焦激光扫描显微镜确定SRC-3的定位。应用蛋白质免疫印迹法（Western blot）和逆转录-聚合酶链反应（RT-PCR）技术评估SRC-3的表达。
GA在体外对A549细胞具有显著的增殖抑制作用，并呈时间和剂量依赖性诱导细胞凋亡。24小时的半数抑制浓度（IC50）值为（3.17±0.13）μmol/L。在A549细胞中发现SRC-3过表达，而GA诱导的A549细胞中SRC-3蛋白和mRNA表达水平呈剂量依赖性显著下调。SRC-3主要定位于细胞核。
GA对人肺腺癌A549细胞具有强大的增殖抑制和凋亡诱导作用，这可能与SRC-3表达下调有关。因此，GA有望成为肺癌治疗的新型靶向药物。
