Ras Inhibition in Glioblastoma Down-regulates Hypoxia-Inducible Factor-1α, Causing Glycolysis Shutdown and Cell Death
作者： Jasmine Jacob-Hirsch , Yoel Kloog , Ninette Amariglio , Gideon Rechavi , Roy Blum
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摘要: Active Ras and phosphatidylinositol-3-kinase–dependent pathways contribute to the malignant phenotype of glioblastoma multiformes (GBM). Here we show that inhibitor trans -farnesylthiosalicylic acid (FTS) exhibits profound antioncogenic effects in U87 GBM cells. FTS inhibited active attenuated signaling extracellular signal-regulated kinase, phosphatidylinositol-3-kinase, Akt. Concomitantly, hypoxia-inducible factor 1α (HIF-1α) disappeared, expression key glycolysis pathway enzymes other HIF-1 α –regulated genes (including vascular endothelial growth Glut-1 glucose transporter) was down-regulated, halted. This led a dramatic reduction ATP, resulting severe energy crisis. In addition, E2F-regulated down-regulated FTS-treated Consequently, cell arrested cells died. These results is potent down-regulator HIF-1α might therefore block invasiveness, survival, angiogenesis GBM.
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