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AKT/mTOR信号通路参与了丹酚酸B诱导的肝癌细胞自噬和凋亡过程。

AKT/mTOR signaling pathway is involved in salvianolic acid B-induced autophagy and apoptosis in hepatocellular carcinoma cells.

作者信息

Gong Ling, Di Chunhong, Xia Xiaofang, Wang Jie, Chen Gongying, Shi Junping, Chen Pengshuai, Xu Hui, Zhang Weibing

机构信息

Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.

Department of Laboratory, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.

出版信息

Int J Oncol. 2016 Dec;49(6):2538-2548. doi: 10.3892/ijo.2016.3748. Epub 2016 Oct 24.

Abstract

Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.

摘要

中药正成为新一代颇具吸引力的抗癌药物。在此,我们探究了丹参主要水溶性成分丹酚酸B(Sal B)对人肝癌细胞(HCC)凋亡和自噬的影响。我们还研究了相关分子机制。我们发现,Sal B具有以浓度依赖性方式抑制肝癌细胞活力的强大能力,并通过线粒体凋亡途径诱导细胞凋亡。此外,Sal B还可诱导自噬。此外,用自噬抑制剂氯喹或3 - 甲基腺嘌呤预处理显示出减弱Sal B诱导的凋亡率的潜力。从机制上讲,Sal B处理在体外抑制了AKT/mTOR信号级联反应。AKT的过表达消除了Sal B对肝癌细胞的影响,表明AKT/mTOR信号通路在Sal B诱导的生物学效应中起关键作用。我们的结果表明,线粒体途径参与了Sal B诱导的肝癌细胞凋亡。此外,AKT/mTOR信号通路参与了Sal B诱导的自噬,而自噬促进了细胞凋亡。本研究可能为将Sal B用作肝癌患者的化疗药物提供一种有前景的策略。

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