Akt Signaling Is Associated with the Berberine-Induced Apoptosis of Human Gastric Cancer Cells
Akt Signaling Is Associated with the Berberine-Induced Apoptosis of Human Gastric Cancer Cells
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Akt 信号转导与小檗碱诱导的人胃癌细胞凋亡相关
DOI：
10.1080/01635581.2015.1004733
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发表时间：
2015-04-03
影响因子：
2.9
通讯作者：
Hu, Tianhui
中科院分区：
文献类型：
--
作者：
Yi, Tingting;Zhuang, Luhua;Hu, Tianhui
尽管对小檗碱的抗肿瘤特性进行了广泛的研究，但其潜在的机制仍然知之甚少。在此，我们发现小檗碱可以诱导人胃癌细胞的细胞凋亡，并且小檗碱处理后的胃癌细胞中切割的聚ADP-核糖聚合酶和caspase-3的表达水平增加，线粒体膜电位（Δψm）受损。进一步研究表明Akt相关的线粒体途径可能部分参与了小檗碱诱导的人胃癌细胞凋亡。小檗碱对BGC-823细胞Akt/mTOR/p70 S6/S6通路有抑制作用。同时，小檗碱可显著抑制Akt的活化，抑制人胃癌裸鼠移植瘤的生长。因此，我们的研究结果揭示了Akt信号通路可能参与小檗碱诱导胃癌细胞凋亡的潜在机制，并可能代表小檗碱作为抗癌剂的重要分子基础。
Despite extensive studies on the antitumor properties of berberine, a small molecule derived from Coptidis rhizoma (Huanglian in Chinese) and many other plants, the underlying mechanism remains poorly understood. Here, we found that berberine-induced cell apoptosis in human gastric cancer cells with the increase of the expression level of cleaved poly ADP-ribose polymerase and caspase-3, and the impairment of mitochondrial membrane potential (Δψm) in berberine-treated gastric cancer cells. In our further studies, the results demonstrated that Akt-related mitochondrial pathway may partly involve in the berberine-induced apoptosis in human gastric cancer cells. Moreover, berberine inhibited the Akt/mTOR/p70S6/S6 pathway in berberine-treated BGC-823 cells. Meanwhile, berberine significantly inhibited the activation of Akt and suppressed tumor growth in xenograft nude mice injected with human gastric cancer cells. Thus, our findings reveal that the underlying mechanism that Akt signaling may contribute to berberine-induced cell apoptosis in gastric cancer cells and might represent an important molecular basis for berberine to act as an anticancer agent.