Resveratrol inhibits VEGF-induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation

白藜芦醇通过调节 PKM2 核转位抑制 VEGF 诱导的人类内皮细胞血管生成,并与有氧糖酵解抑制有关

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作者:Hongyan Wu, Liwei He, JingJing Shi, Xianbang Hou, Hongjiang Zhang, Xiaoping Zhang, Qing An, Fangtian Fan

Abstract

Endothelial cells (ECs) mainly depend on aerobic glycolysis to generate angiogenesis. Deregulation of glycolysis is often observed in human endothelial cells during angiogenesis. In the present study, we first report that resveratrol (RST), which has been intensively studied in glucose metabolism of various cancer cells, has a profound inhibitory effect on tube formation and migration via suppression of glycolysis in human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor (VEGF). Moreover, we further reveal that RST reduced the mRNA and protein level of glucose transporter-1(GLUT1), hexokinase II (HK2), phosphofructokinase-1(PFK1) and pyruvate kinase M2 (PKM2) through modulation of ERK-mediated PKM2 nuclear translocation. Our results provide a novel mechanism to account for the inhibition of RST on VEGF-mediated angiogenesis and suggest that targeting aerobic glycolysis or nuclear PKM2 may be a new approach for pathological angiogenesis prevention or treatment.

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