冬凌草甲素诱导胃癌BGC-823细胞凋亡及G2/M细胞周期阻滞作用研究

冬凌草甲素诱导胃癌BGC-823细胞凋亡及G₂/M细胞周期阻滞作用研究

韩健, 叶敏, 乔雪, 吴婉莹, 曲桂芹, 果德安^*

北京大学药学院天然药物及仿生药物国家重点实验室, 北京100083

收稿日期:2007-05-20 修回日期:2007-11-10 出版日期:2007-12-15 发布日期:2007-12-15
通讯作者: 果德安*

Induction of apoptosis and G₂/M cell cycle arrest by oridonin in human gastric cancer BGC-823 cells

Jian Han, Min Ye, Xue Qiao, Wan-Ying Wu, Gui-Qin Qu, De-An Guo^*

The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Received:2007-05-20 Revised:2007-11-10 Online:2007-12-15 Published:2007-12-15
Contact: De-An Guo*

摘要/Abstract

摘要： 目的研究冬凌草甲素体外诱导胃癌BGC-823细胞凋亡和细胞周期阻滞的作用, 阐明其作用机理,为临床应用提供科学依据。方法用MTT方法测定冬凌草甲素体外抑制BGC-823细胞生长的作用。用共聚焦荧光显微镜和流式细胞仪分别观察诱导凋亡的情况。线粒体膜电位和细胞内钙离子浓度分别用荧光探针标记后流式细胞仪测定。凋亡和细胞周期相关蛋白的表达用Western blotting进行测定。结果冬凌草甲素对BGC-823细胞的半数生长抑制浓度IC50值为22.21μmol·L^-1, 并诱导细胞凋亡, 呈现浓度依赖性。此外, 能够降低线粒体膜电位, 升高细胞内钙离子浓度, 激活caspase-3前体。同时, 冬凌草甲素能够使得BGC-823细胞阻滞在细胞周期的G2/M期, 伴随有cyclin A蛋白的表达下降。在发生凋亡和细胞阻滞之前, 观察到p53蛋白的表达增加。结论冬凌草甲素能够诱导BGC-823细胞产生凋亡, 并使细胞周期阻滞在G2/M期。其凋亡机理与caspase-3的激活, p53蛋白表达上调及cyclin A表达下调相关。

关键词: 冬凌草甲素, 冬凌草甲素, 冬凌草甲素, 人胃癌细胞BGC-823, 人胃癌细胞BGC-823, 人胃癌细胞BGC-823, 凋亡, 凋亡, 凋亡, 细胞周期阻滞, 细胞周期阻滞, 细胞周期阻滞, p53, p53, p53, Cyclin A, Cyclin A, Cyclin A

Abstract:

Aim To investigate in vitro apoptosis-induction effects of oridonin on gastric tumor cells BGC-823 and its effects on cell cycle, mitochondrial membrane potential and intracellular Ca²⁺ to shed light on the mode of its anticancer action. Methods The MTT method was used to investigate the inhibitory effect of oridonin on BGC-823 cells. The apoptosis-induction effect was evaluated by confocal laser microscopy and flow cytometry. The change of mitochondrial membrane potential and the increase of intracellular Ca²⁺ were assessed by fluorescence probe rhodamine123 and Fluo 3-AM, respectively, with flow cytometry. The expression of apoptosis and cell cycle related proteins was studied using western blotting. Results Oridonin inhibited BGC-823 cells growth with IC₅₀ of 22.21 μmol·L^-1. It induced apoptosis in a dose-dependent manner. In addition, it decreased mitochondria membrane potential, increased intracellular Ca²⁺, and activated pro-caspase 3. BGC-823 cells were arrested in G2/M cell cycle phase with lower expression of cyclin A protein. The up-regulation of p53 was observed before apoptosis and cell cycle arrest occurred. Conclusion Oridonin inhibits the proliferation of BGC-823 cells through G2/M cell cycle arrest and apoptosis induction, which is mediated by influx of Ca²⁺, up-regulation of p53, activation of caspase-3, and down-regulation of cyclin A.

Key words: Oridonin, Oridonin, Human gastric cancer, Human gastric cancer, Apoptosis, Apoptosis, Cell cycle arrest, Cell cycle arrest, p53, p53, Cyclin A, Cyclin A

中图分类号:

R965

Supporting: Foundation item: Program for Changjiang Scholar and Innovative Team in University (Grant No. 985-2-063-112).
^*Corresponding author. Tel.: 86-10-82801516; fax: 86-10-82802700

韩健, 叶敏, 乔雪, 吴婉莹, 曲桂芹, 果德安^*

. 冬凌草甲素诱导胃癌BGC-823细胞凋亡及G₂/M细胞周期阻滞作用研究[J]. .

Jian Han, Min Ye, Xue Qiao, Wan-Ying Wu, Gui-Qin Qu, De-An Guo^*. Induction of apoptosis and G₂/M cell cycle arrest by oridonin in human gastric cancer BGC-823 cells[J]. .

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冬凌草甲素诱导胃癌BGC-823细胞凋亡及G₂/M细胞周期阻滞作用研究

Induction of apoptosis and G₂/M cell cycle arrest by oridonin in human gastric cancer BGC-823 cells

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