Abstract
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.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 30701032, 30472044, 90713038 and 30973556), International Corporation Program of China (2008DFA32120), and Natural Science Foundation of Jiangsu province (No. BK2009297).
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We declare that there are no conflicts of interest.
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Y. Gao and N. Lu contributed equally to this work.
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Gao, Y., Lu, N., Ling, Y. et al. Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation. J Cancer Res Clin Oncol 136, 667–675 (2010). https://doi.org/10.1007/s00432-009-0705-2
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DOI: https://doi.org/10.1007/s00432-009-0705-2