PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis

doi:10.1016/j.bcp.2018.01.051

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis
	Fang, Xiaona 3; Xie, Hua2 ; Luo, Min 3; Chen, Zhen 3; Wang, Fang 3; Li, Qingshan 1; Wang, Xiaokun 3; Ding, Jian2 ; Fu, Liwu 3
刊名	BIOCHEMICAL PHARMACOLOGY
	2018-04
卷号	150 页码:131-140
关键词	Angiogenesis And-tumor activity Multi-tyrosine kinases inhibitor PBA2 VEGFR2
ISSN号	0006-2952
DOI	10.1016/j.bcp.2018.01.051
文献子类	Article
英文摘要	VEGFR2 (vascular endothelial growth factor receptor 2) is the main trigger of VEGF-mediated angiogenic signal and targeting VEGFR2 pathway to inhibit tumor angiogenesis represents a promising strategy for cancer therapy. We elucidated that a novel compound, PBA2 exhibited potent anti-tumor effects both in vitro and in vivo with limited toxicity. ELISA assay revealed that PBA2 had a strong suppressive activity against VEGFR2 related to angiogenesis. Furthermore, PBA2 considerably disrupted tube formation of endothelial cells in vitro and systemic administration of PBA2 exerted decreased tumor angiogenesis in vivo. Functional tests demonstrated that PBA2 concentration-dependently impeded the migration and proliferation of endothelial cells. PBA2 had no effects on the expression level of VEGF both in the detected cancer cells and endothelial cells. VEGFR2 and its downstream Akt and Erk pathways were blocked by PBA2 in a concentration-dependent manner both in vitro and in vivo. Overall, we first demonstrated that PBA2, targeting VEGFR2 related to angiogenesis, presented remarkable antiangiogenic and anti-tumor activities through attenuating VEGFR2 mediated pathway in vitro and in vivo with limited toxicity. These observations posed that PBA2 could be a potential drug candidate for developing antiangiogenic tyrosine kinase inhibitor in cancer therapy.
资助项目	Natural Scientific Foundation of China[81473233] ; Natural Scientific Foundation of Guangdong Province[2016A030312014] ; Science and Technology Planning Project of Guangdong Esophageal Cancer Research Institute[Q201514] ; Science and Technology project of Guangdong Province[2014B050504004] ; Science and Technology project of Guangdong Province[2013B051000046]
WOS关键词	SMALL-MOLECULE INHIBITORS ; GROWTH-FACTOR ; IN-VITRO ; CHEMOTHERAPEUTIC-AGENTS ; CANCER ; THERAPY ; IDENTIFICATION ; ACTIVATION ; MECHANISMS ; KINASES
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000431287100013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279818]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian; Fu, Liwu
作者单位	1.Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Hematol, Guangzhou 510180, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Sun Yat Sen Univ, Guangdong Esophageal Canc Inst, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China;
推荐引用方式 GB/T 7714	Fang, Xiaona,Xie, Hua,Luo, Min,et al. PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis[J]. BIOCHEMICAL PHARMACOLOGY,2018,150:131-140.
APA	Fang, Xiaona.,Xie, Hua.,Luo, Min.,Chen, Zhen.,Wang, Fang.,...&Fu, Liwu.(2018).PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis.BIOCHEMICAL PHARMACOLOGY,150,131-140.
MLA	Fang, Xiaona,et al."PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis".BIOCHEMICAL PHARMACOLOGY 150(2018):131-140.