Department of Oncology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China ; Department of Interventional Radiology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
Cancer Cell Int. 2014 Jun 11;14:49. doi: 10.1186/1475-2867-14-49. eCollection 2014.
Hepatocellular carcinoma (HCC), the primary liver cancer, is one of the most malignant human tumors with extremely poor prognosis. The aim of this study was to investigate the anti-cancer effect of berberine in a human hepatocellular carcinoma cell line (HepG2), and to study the underlying mechanisms by focusing on the AMP-activated protein kinase (AMPK) signaling cascade.
We found that berberine induced both apoptotic and autophagic death of HepG2 cells, which was associated with a significant activation of AMPK and an increased expression of the inactive form of acetyl-CoA carboxylase (ACC). Inhibition of AMPK by RNA interference (RNAi) or by its inhibitor compound C suppressed berberine-induced caspase-3 cleavage, apoptosis and autophagy in HepG2 cells, while AICAR, the AMPK activator, possessed strong cytotoxic effects. In HepG2 cells, mammalian target of rapamycin complex 1 (mTORC1) activation was important for cell survival, and berberine inhibited mTORC1 via AMPK activation.
Together, these results suggested that berberine-induced both apoptotic and autophagic death requires AMPK activation in HepG2 cells.
肝细胞癌（HCC）是原发性肝癌，是最具恶性的人类肿瘤之一，预后极差。本研究旨在探讨小檗碱在人肝癌细胞系（HepG2）中的抗癌作用，并通过关注 AMP 激活的蛋白激酶（AMPK）信号级联来研究其潜在机制。
我们发现小檗碱诱导 HepG2 细胞凋亡和自噬死亡，这与 AMPK 的显著激活和乙酰辅酶 A 羧化酶（ACC）无活性形式的表达增加有关。RNA 干扰（RNAi）或其抑制剂化合物 C 抑制 AMPK 可抑制小檗碱诱导的 caspase-3 切割、凋亡和自噬，而 AMPK 激活剂 AICAR 则具有很强的细胞毒性作用。在 HepG2 细胞中，雷帕霉素复合物 1（mTORC1）的激活对于细胞存活很重要，小檗碱通过 AMPK 激活抑制 mTORC1。
综上所述，这些结果表明小檗碱诱导的 HepG2 细胞凋亡和自噬死亡需要 AMPK 的激活。
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