Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation

Purpose In this study, we examined the antiangiogenic effect of oroxylin A in vitro and in vivo and explored the potential mechanisms for this effect. Methods Transwell assay and tube formation assay were used to evaluate the effects of oroxylin A on vascular endothelial growth factor (VEGF)-induced migration and tube formation of human umbilical vein endothelial cells (HUVECs). Rat aortic ring assay was also employed to assess the effect of oroxylin A on microvessel outgrowth from rat aorta. Human tumor xenografts model in nude mice was further used to investigate the antiangiogenic activity of oroxylin A in vivo. Western blot analysis was used to investigate the related mechanism. Results Oroxylin A remarkably suppressed the VEGF-stimulated migration and tube formation of HUVECs. It also inhibited microvessel sprouting from rat aortic ring in vitro . In addition, it suppressed the angiogenesis of xenograft tumor in nude mice, which concurred with the inhibition of tumor growth. Moreover, oroxylin A blocked VEGF-induced phosphorylation of KDR/Flk-1 and related downstream signaling molecules, including p38 mitogen-activated protein kinase, extracellular signal-regulated kinase and Akt. Conclusion Oroxylin A possessed antiangiogenic activities in vitro and in vivo, which could be an underlying mechanism of its anticancer effect.