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Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1
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.
Insights
Oroxylin A demonstrates significant antiangiogenic properties, inhibiting blood vessel formation both in lab tests and in living organisms. This compound
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Angiogenesis is crucial for tumor growth and metastasis.
- Targeting angiogenesis is a key strategy in cancer therapy.
- Oroxylin A is a natural compound with potential therapeutic applications.
Purpose of the Study:
- To investigate the antiangiogenic effects of oroxylin A.
- To explore the underlying mechanisms of oroxylin A's antiangiogenic activity.
- To evaluate oroxylin A's potential as an anticancer agent.
Main Methods:
- In vitro assays: Transwell migration, tube formation, and rat aortic ring assays.
- In vivo studies: Human tumor xenografts in nude mice.
- Mechanism exploration: Western blot analysis of signaling pathways.
Main Results:
- Oroxylin A significantly inhibited VEGF-induced endothelial cell migration and tube formation.
- Oroxylin A suppressed microvessel outgrowth in rat aortic rings and angiogenesis in vivo.
- Oroxylin A reduced tumor growth in xenograft models and blocked key signaling pathways (KDR/Flk-1, p38 MAPK, ERK, Akt).
Conclusions:
- Oroxylin A exhibits potent antiangiogenic activity in vitro and in vivo.
- The antiangiogenic effects of oroxylin A contribute to its observed anticancer properties.
- Oroxylin A represents a promising therapeutic candidate for targeting angiogenesis in cancer.
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