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

被引:64
|
作者
Gong, Ling [1 ]
Di, Chunhong [2 ]
Xia, Xiaofang [1 ]
Wang, Jie [1 ]
Chen, Gongying [1 ]
Shi, Junping [1 ]
Chen, Pengshuai [3 ]
Xu, Hui [3 ]
Zhang, Weibing [3 ]
机构
[1] Hangzhou Normal Univ, Affiliated Hosp, Dept Liver Dis, Hangzhou 310015, Zhejiang, Peoples R China
[2] Hangzhou Normal Univ, Affiliated Hosp, Dept Lab, Hangzhou 310015, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Dept Pharm, Affiliated Hosp 1, 2 NanBai Xiang, Wenzhou 325000, Zhejiang, Peoples R China
关键词
hepatocellular carcinoma; salvianolic acid B; AKT/mTOR signaling; apoptosis; autophagy; CANCER CELLS; CYTOCHROME-C; IN-VITRO; MILTIORRHIZA; IMMUNOTHERAPY; CHEMOTHERAPY; MODULATION; INHIBITION; SORAFENIB; DISEASE;
D O I
10.3892/ijo.2016.3748
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2538 / 2548
页数:11
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