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

Summary Endothelial cells ( EC s) 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 ( HUVEC s) induced by vascular endothelial growth factor ( VEGF ). Moreover, we further reveal that RST reduced the mRNA and protein level of glucose transporter‐1( GLUT 1), hexokinase II ( HK 2), phosphofructokinase‐1( PFK 1) and pyruvate kinase M2 ( PKM 2) through modulation of ERK ‐mediated PKM 2 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 PKM 2 may be a new approach for pathological angiogenesis prevention or treatment.