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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 …