Research Papers:

Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway

Ning Tang, Lei Shi, Zhenlong Yu, Peipei Dong, Chao Wang, Xiaokui Huo, Baojing Zhang, Shanshan Huang, Sa Deng, Kexin Liu, Tonghui Ma, Xiaobo Wang, Lijun Wu and Xiaochi Ma _

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Oncotarget. 2016; 7:3533-3547. https://doi.org/10.18632/oncotarget.6514

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Ning Tang1,*, Lei Shi2,*, Zhenlong Yu1,4,*, Peipei Dong1, Chao Wang1, Xiaokui Huo1, Baojing Zhang1, Shanshan Huang1, Sa Deng1, Kexin Liu1, Tonghui Ma3, Xiaobo Wang4, Lijun Wu4, Xiao-Chi Ma1,4

1College of Pharmacy, Academy of Integrative Medicine, Key Laboratory of Pharmacokinetic and Drug Transport of Liaoning, Dalian Medical University, Dalian, China

2Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China

3College of Basic Medical Science, Dalian Medical University, Dalian, China

4Department of Pharmacy and Traditional Chinese medicine, Chinese People’s Liberation Army 210 Hospital, Dalian, China

*These authors have contributed equally to this work

Correspondence to:

Xiao-Chi Ma, e-mail: maxc1978@163.com

Keywords: gamabufotalin, angiogenesis, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), aortic ring

Received: August 18, 2015     Accepted: November 21, 2015     Published: December 09, 2015


Gamabufotalin (CS-6), a main active compound isolated from Chinese medicine Chansu, has been shown to strongly inhibit cancer cell growth and inflammatory response. However, its effects on angiogenesis have not been known yet. Here, we sought to determine the biological effects of CS-6 on signaling mechanisms during angiogenesis. Our present results fully demonstrate that CS-6 could significantly inhibit VEGF triggered HUVECs proliferation, migration, invasion and tubulogenesis in vitro and blocked vascularization in Matrigel plugs impregnated in C57/BL6 mice as well as reduced vessel density in human lung tumor xenograft implanted in nude mice. Computer simulations revealed that CS-6 interacted with the ATP-binding sites of VEGFR-2 using molecular docking. Furthermore, western blot analysis indicated that CS-6 inhibited VEGF-induced phosphorylation of VEGFR-2 kinase and suppressed the activity of VEGFR-2-mediated signaling cascades. Therefore, our studies demonstrated that CS-6 inhibited angiogenesis by inhibiting the activation of VEGFR-2 signaling pathways and CS-6 could be a potential candidate in angiogenesis-related disease therapy.

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