RT Journal Article SR Electronic T1 9-β-d-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 178 OP 186 DO 10.1124/mol.66.1.178 VO 66 IS 1 A1 Jing Fang A1 Zongxian Cao A1 Yi Charlie Chen A1 Eddie Reed A1 Bing-Hua Jiang YR 2004 UL http://molpharm.aspetjournals.org/content/66/1/178.abstract AB Ovarian cancer is the leading cause of death from gynecological malignancy and has the worst prognosis of all gynecological cancers. Vascular endothelial growth factor (VEGF) plays an important role in ovarian cancer development. 9-β-d-Arabinofuranosyl-2-fluoroadenine (Fara-A), a nucleotide analog, is frequently used in treating certain types of cancer. However, the effectiveness of Fara-A on ovarian cancer cells is unknown. In this study, we found that Fara-A inhibited VEGF expression in human ovarian cancer cells. Fara-A inhibited VEGF transcriptional activation through hypoxia-inducible factor 1 (HIF-1). HIF-1 is composed of HIF-1α and -1β subunits. Fara-A inhibited expression of HIF-1α but not HIF-1β. Overexpression of HIF-1α reversed Fara-A-inhibited VEGF transcriptional activation. Our results demonstrated that Fara-A inhibited VEGF transcriptional activation through HIF-1α expression. Fara-A partly inhibited HIF-1α mRNA levels. Fara-A blocked the activation of AKT but not of ERK1/2. Overexpression of AKT reversed the Fara-A-inhibited VEGF transcriptional activation, suggesting that Fara-A inhibits VEGF expression via phosphatidylinositol 3-kinase/AKT signaling. These results demonstrate a new function of Fara-A in inhibiting VEGF and HIF-1α expression and identify a potential molecular mechanism of the regulation.