Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway

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• 作者：Manmei Li^a ; ¹ ; Shuai Wu^a ; ¹ ; Zhong Liu^b ; Wei Zhang^a ; Jing Xu^c ; Ying Wang^a ; Junshan Liu^a ; Dongmei Zhang^a ; Haiyan Tian^a ; Yaolan Li^a ; ^{tliyl@jnu.edu.cn} ; Wencai Ye^a ; ^{chywc@yahoo.com.cn}
• 关键词：HUVECs ; human umbilical vein endothelial cells ; VEGF ; vascular endothelial growth factor ; VEGFR-2 ; vascular endothelial growth factor receptor 2 ; RTK ; receptor tyrosine kinase ; DMSO ; dimethyl sulphoxide ; VEGFR-1 ; vascular endothelial growth factor recepto
• 刊名：Biochemical Pharmacology
• 出版年：2012
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：1 May, 2012
• 卷：83
• 期：9
• 页码：1251-1260
• 文件大小：1567 K

摘要

Angiogenesis is crucial for carcinogenesis and other angiogenic processes. Arenobufagin, one of the major components of toad venom, is a traditional Chinese medicine used for cancer therapy. It inhibits cell growth in several cancer cell lines. However, little is known about arenobufagin's anti-angiogenic activity. In this study, we showed that arenobufagin inhibited vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Arenobufagin also suppressed sprouting formation from VEGF-treated aortic rings in an ex vivo model. Furthermore, we found that arenobufagin blocked angiogenesis in a matrigel plugs assay. Computer simulations suggested that arenobufagin interacted with the ATP-binding sites of VEGFR-2 by docking. In addition, arenobufagin inhibited VEGF-induced VEGFR-2 auto-phosphorylation and suppressed the activity of VEGFR-2-mediated signaling cascades. Taken together, our findings demonstrate that arenobufagin is a specific inhibitor of VEGF-mediated angiogenesis.