TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFR beta

doi:10.4161/cbt.5.3.2543

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

	TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFR beta
	Zhong, L ; Guo, XN ; Zhang, XH ; Sun, QM ; Tong, LJ ; Wu, ZX ; Luo, XM; Jiang, HL; Nan, FJ; Zhang, XW
刊名	CANCER BIOLOGY & THERAPY
	2006-03
卷号	5 期号:3 页码:323-330
关键词	tyrosine kinase VEGFR2 PDGFR beta angiogenesis
ISSN号	1538-4047
DOI	10.4161/cbt.5.3.2543
文献子类	Article
英文摘要	Tyrosine kinases have been strongly implicated as therapeutic targets that influence the angiogenic process in growing tumors. In this study, we revealed that TKI-31 is a potent broad spectrum tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFR beta) and also inhibits kinases of other class, such as c-Kit and c-Src on molecular base, but showed no activity against vascular endothelial growth factor receptor 1 (VEGFR1) and epidermal growth factor receptor ( EGFR). TKI-31 inhibits VEGF-induced phosphorylation of VEGFR2 in endothelial cells as well as PDGFBB-induced phosphorylation in fibroblast cells, and leading to the inhibition of down-stream signaling triggered by these receptors such as PI3K/Akt/mTOR, MAPK42/44( ERK) and paxillin. TKI-31 also inhibited VEGF-induced endothelial cells proliferation, migration and their differentiation into capillary-like tube formation. Its anti-angiogenic property was further confirmed by the inhibition of neovascularization on CAM, in vivo. These results collectively highlight the therapeutic potential of this compound for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
WOS关键词	ENDOTHELIAL GROWTH-FACTOR ; TYROSINE KINASE ; TUMOR ANGIOGENESIS ; TUBE FORMATION ; CANCER ; EXPRESSION ; SURVIVAL
WOS研究方向	Oncology
语种	英语
出版者	LANDES BIOSCIENCE
WOS记录号	WOS:000237608800023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273657]
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, J
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol,State Key Lab Drug Res, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Chinese Natl Ctr Drug Screening, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Zhong, L,Guo, XN,Zhang, XH,et al. TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFR beta[J]. CANCER BIOLOGY & THERAPY,2006,5(3):323-330.
APA	Zhong, L.,Guo, XN.,Zhang, XH.,Sun, QM.,Tong, LJ.,...&Ding, J.(2006).TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFR beta.CANCER BIOLOGY & THERAPY,5(3),323-330.
MLA	Zhong, L,et al."TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFR beta".CANCER BIOLOGY & THERAPY 5.3(2006):323-330.