PTEN公司
抗辐射性
癌症研究
蛋白激酶B
张力素
岩白菜素
糖酵解
生物
合成致死
癌细胞
癌症
PI3K/AKT/mTOR通路
化学
细胞凋亡
生物化学
酶
细胞培养
DNA修复
基因
遗传学
有机化学
作者
Xiaoying Li,Li Xie,Zhou Li,Yu Gan,Shuangze Han,Yuanfeng Zhou,Qing Xiang,Wei Li
标识
DOI:10.1142/s0192415x23500842
摘要
Hexokinase 2 (HK2), the first glycolytic rate-limiting enzyme, is closely correlated with the occurrence and progression of tumors. Effective therapeutic agents targeting HK2 are urgently needed. Bergenin has exhibited various pharmacological activities, such as antitumor properties. However, the effects of bergenin on the abnormal glucose metabolism of cancer cells are yet unclear. In this study, HK2 was overexpressed in OSCC tissues, and the depletion of HK2 inhibited the growth of OSCC cells in vitro and in vivo. Moreover, these results showed that the natural compound, bergenin, exerted a robust antitumor effect on OSCC cells. Bergenin inhibited cancer cell proliferation, suppressed glycolysis, and induced intrinsic apoptosis in OSCC cells by downregulating HK2. Notably, bergenin restored the antitumor efficacy of irradiation in the radioresistant OSCC cells. A mechanistic study revealed that bergenin upregulated the protein level of phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) by enhancing the interaction between PTEN and ubiquitin-specific protease 13 (USP13) and stabilizing PTEN; this eventually inhibited AKT phosphorylation and HK2 expression. Bergenin was identified as a novel therapeutic agent against glycolysis to inhibit OSCC and overcome radioresistance. Targeting PTEN/AKT/HK2 signaling could be a promising option for clinical OSCC treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI