文献类型：期刊文献

英文题名：Salvanic acid B inhibits glycolysis in oral squamous cell carcinoma via targeting PI3K/AKT/HIF-1α signaling pathway

作者：Wei, Jie[1];Wu, Jun[2];Xu, Wen[3,4];Nie, Hong[5];Zhou, Ruiqing[1];Wang, Rui[4];Liu, Yang[6];Tang, Guoyao[1];Wu, Jianyong[1]

机构：[1]Shanghai Jiao Tong Univ, Xin Hua Hosp, Dept Stomatol, Sch Med, Shanghai 200092, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Lab Med, Shanghai 200080, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[5]Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Dept Immunol & Microbol, Sch Med, Shanghai 200025, Peoples R China;[6]Nanjing Med Univ, Wuxi Peoples Hosp, Dept Somatol, Wuxi 214023, Peoples R China

年份：2018

卷号：9

外文期刊名：CELL DEATH & DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000433092300019)】；

基金：This work was supported by the National Natural Science Foundation of China under grant numbers of NSCF 81400514 and 81401956, National Key Technology Research and Development Program under grant numbers 2014BAI09B03.

语种：英文

摘要：Our previous study demonstrated a progressive glycolytic perturbation during the course of DMBA-induced hamster oral carcinogenesis, which was attenuated by salvianolic acid B (Sal-B) treatment along with decreased incidences of oral squamous cell carcinoma (OSCC) formation. It was proposed that metabolic modulation should be an additional mode of action attributable to Sal-B's anti-carcinogenic activity. However, the molecular mechanisms underlying Sal-B-induced metabolic modulation function remained elusive. In the present study, we performed next-generation sequencing (NGS) profiling in the same animal model and found Sal-B treatment evoked a general downregulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and hypoxia inducible factor 1a subunit (HIF-1 alpha) signaling pathways, which might contribute to Sal-B's metabolic modulation activity. The inhibitory effects of Sal-B on aerobic glycolysis, as well as PI3K/AKT and HIF-1 alpha signaling pathways, were validated in two well-characterized OSCC cell lines (Cal27 and HN4), and premalignant oral Leuk1 cells and Sal-B treatment led to elevation of the loss of mitochondrial membrane potential (MMP), increased cell apoptosis, and reduced abilities of colony formation. Rescue assays suggested that compared with Sal-B treatment group, Akt or hif-1a overexpression attenuated the inhibitory effect of Sal-B on glucose uptake and intracellular lactate level. Taken together, our results suggested that Sal-B modulated aberrant glucose metabolism via the PI3K/AKT/HIF-1 alpha signaling pathways, which might contribute to the anti-carcinogenic activity of Sal-B.