Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation
Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation
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Oroxylin A 通过阻断血管内皮生长因子诱导的 KDR/Flk-1 磷酸化来抑制血管生成
DOI：
10.1007/s00432-009-0705-2
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Guo, Qinglong
中科院分区：
文献类型：
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作者：
Gao, Ying;Lu, Na;Guo, Qinglong
目的本研究通过体外和体内实验观察了木脂素A（oroxylin A）对血管内皮生长因子（vascular endothelial growth factor，VEGF）诱导的人脐静脉内皮细胞（human umbilical vein endothelial cells，HUVECs）迁移和管腔形成的影响，并探讨其可能的作用机制。还采用大鼠主动脉环测定来评估木脂素A对来自大鼠主动脉的微血管生长的影响。进一步采用裸鼠人肿瘤移植瘤模型研究了木脂素A的体内抗血管生成活性。结果Oroxylin A可明显抑制VEGF诱导的HUVECs迁移和管腔形成。在体外实验中，它还能抑制大鼠主动脉环微血管的出芽，并能抑制裸鼠移植瘤的血管生成，这与抑制肿瘤生长是一致的。此外，Oroxylin A还能阻断VEGF诱导的KDR/Flk-1及相关下游信号分子p38丝裂原活化蛋白激酶、细胞外信号调节激酶和Akt的磷酸化。结论Oroxylin A在体内外均具有抗血管生成活性，这可能是其抗肿瘤作用的机制之一。
PurposeIn this study, we examined the antiangiogenic effect of oroxylin A in vitro and in vivo and explored the potential mechanisms for this effect.MethodsTranswell 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.ResultsOroxylin 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.ConclusionOroxylin A possessed antiangiogenic activities in vitro and in vivo, which could be an underlying mechanism of its anticancer effect.