通过降低己糖激酶2，白藜芦醇可诱导依赖有氧糖酵解的肝癌细胞凋亡，并抑制小鼠肿瘤生长。

By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice.

作者信息

Dai Weiqi, Wang Fan, Lu Jie, Xia Yujing, He Lei, Chen Kan, Li Jingjing, Li Sainan, Liu Tong, Zheng Yuanyuan, Wang Jianrong, Lu Wenxia, Zhou Yuqing, Yin Qin, Abudumijiti Huerxidan, Chen Rongxia, Zhang Rong, Zhou Li, Zhou Zheng, Zhu Rong, Yang Jing, Wang Chengfen, Zhang Huawei, Zhou Yingqun, Xu Ling, Guo Chuanyong

机构信息

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; The First Clinical Medical College of Nanjing Medical University, Nanjing, China.

出版信息

Oncotarget. 2015 May 30;6(15):13703-17. doi: 10.18632/oncotarget.3800.

Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis. Aerobic glycolysis was observed in four HCC cell lines compared to the normal hepatic cells. Resveratrol sensitized aerobic glycolytic HCC cells to apoptosis, and this effect was attenuated by glycolytic inhibitors. The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells. In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells. Combination treatment with both reagents inhibited the growth and promoted apoptosis of HCC-bearing mice. The reduction of HK2 by resveratrol provides a new dimension to clinical HCC therapies aimed at preventing disease progression.

癌细胞表现出一种被称为有氧糖酵解的代谢表型改变。己糖激酶2（HK2）的表达改变细胞的代谢表型以支持癌性生长。在本研究中，我们研究了白藜芦醇对HK2表达和肝细胞癌（HCC）细胞糖酵解的抑制作用。与正常肝细胞相比，在四种HCC细胞系中观察到有氧糖酵解。白藜芦醇使有氧糖酵解的HCC细胞对凋亡敏感，并且这种作用被糖酵解抑制剂减弱。线粒体凋亡的诱导与白藜芦醇使HCC细胞中HK2表达降低有关。此外，白藜芦醇增强了索拉非尼对有氧糖酵解的HCC细胞生长的抑制作用。两种试剂联合治疗抑制了荷HCC小鼠的生长并促进了其凋亡。白藜芦醇降低HK2水平为旨在预防疾病进展的临床HCC治疗提供了新的维度。