Song Xiaoling, Wang Zheng, Liang Haibin, Zhang Wenjie, Ye Yuanyuan, Li HuaiFeng, Hu Yunping, Zhang Yijian, Weng Hao, Lu Jianhua, Wang Xuefeng, Li Maolan, Liu Yingbin, Gu Jun
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Int J Biol Sci. 2017 Jun 1;13(6):782-793. doi: 10.7150/ijbs.18732. eCollection 2017.
Gallbladder cancer (GBC), highly aggressive form of cancer with an extremely poor prognosis, is the most common malignancy of the biliary tract. In this study, we investigated the effects of dioscin (DSN) on human GBC and the potential mechanisms underlying these effects. The results showed that DSN significantly inhibited GBC cell proliferation and migration. Moreover, DSN induced GBC cell apoptosis via mitochondrial dependent apoptotic signalling. Reactive oxygen species (ROS) and glutathione (GSH) levels were measured, and ROS scavengers completely inhibited DSN-induced apoptosis and migration, indicating that ROS play an essential role in GBC progression. Western blot analysis showed that AKT activity was significantly downregulated after DSN treatment, and that inhibition/ectopic expression of AKT enhanced/abolished DSN-induced apoptosis but not migration. Furthermore, we confirmed the relationship between ROS and the PI3K/AKT pathway and found that DSN induced apoptosis by regulating ROS-mediated PI3K/AKT signaling. Taken together, these findings indicate that DSN induces GBC apoptosis through inhibiting ROS-mediated PI3K/AKT signalling.
胆囊癌（GBC）是胆道最常见的恶性肿瘤，是一种侵袭性很强、预后极差的癌症。在本研究中，我们研究了薯蓣皂苷（DSN）对人胆囊癌的影响及其潜在机制。结果表明，DSN显著抑制胆囊癌细胞的增殖和迁移。此外，DSN通过线粒体依赖性凋亡信号通路诱导胆囊癌细胞凋亡。我们检测了活性氧（ROS）和谷胱甘肽（GSH）水平，发现ROS清除剂完全抑制了DSN诱导的凋亡和迁移，表明ROS在胆囊癌进展中起重要作用。蛋白质免疫印迹分析表明，DSN处理后AKT活性显著下调，抑制/过表达AKT增强/消除了DSN诱导的凋亡，但不影响迁移。此外，我们证实了ROS与PI3K/AKT通路之间的关系，发现DSN通过调节ROS介导的PI3K/AKT信号通路诱导凋亡。综上所述，这些发现表明DSN通过抑制ROS介导的PI3K/AKT信号通路诱导胆囊癌细胞凋亡。
