WSS25 Inhibits Growth of Xenografted Hepatocellular Cancer Cells in Nude Mice by Disrupting Angiogenesis via Blocking Bone Morphogenetic Protein (BMP)/Smad/Id1 Signaling

doi:10.1074/jbc.M110.105544

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	WSS25 Inhibits Growth of Xenografted Hepatocellular Cancer Cells in Nude Mice by Disrupting Angiogenesis via Blocking Bone Morphogenetic Protein (BMP)/Smad/Id1 Signaling
	Qiu, Hong 2; Yang, Bo 1; Pei, Zhi-Chao 2; Zhang, Zhang 2; Ding, Kan2,3
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2010-10-15
卷号	285 期号:42 页码:32638-32646
ISSN号	0021-9258
DOI	10.1074/jbc.M110.105544
文献子类	Article
英文摘要	The highly expressed Id1 (inhibitor of DNA binding/differentiation) protein promotes angiogenesis in HCC and is a well established target for anti-angiogenesis therapeutic strategies. Heparan sulfate (HS) mimetics such as PI-88 can abrogate HS-protein interactions to inhibit angiogenesis. Id1 is the direct downstream effector of bone morphogenetic proteins (BMPs), which are angiogenic and HS-binding proteins. Thus, targeting BMPs by HS mimetics may inhibit angiogenesis via attenuating Id1 expression. We report here that a HS mimetic WSS25 potently inhibited the tube formation of HMEC-1 cells on Matrigel and their migration. Meanwhile, WSS25 (25 mu g/ml) nearly completely blocked Id1 expression in the HMEC-1 cells as demonstrated by oligo-angiogenesis microarray analysis and further confirmed by RT-PCR and Western blotting. BMP/Smad/Id1 signaling also was blocked by WSS25 treatment in HMEC-1 cells. Importantly, Id1 knockdown in HMEC-1 cells caused the disruption of their tube formation on Matrigel. By employing quartz crystal microbalance analysis, we found that WSS25 strongly bound to BMP2. Moreover, WSS25 impaired BMP2-induced tube formation of HMEC-1 cells on Matrigel and angiogenesis in Matrigel transplanted into C57BL6 mice. Furthermore, WSS25 (100 mg/kg) abrogated the growth of HCC cells xenografted in male nude mice. Immunohistochemical analysis showed that both the expression of Id1 and the endothelial cell marker CD31 were lower in the WSS25-treated tumor tissue than in the control. Therefore, WSS25 is a potential drug candidate for HCC therapy as a tumor angiogenesis inhibitor.
资助项目	National Natural Science Foundation of China[30670470] ; National High Technology Research and Development Program (863) of China[2006AA022102] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[07G604F036] ; Chinese Academy of Sciences, China[KSCX1-YW-R-18] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09103-071]
WOS关键词	ENDOTHELIAL-CELLS ; HEPARAN-SULFATE ; BIOLOGICAL-ACTIVITY ; TUMOR ANGIOGENESIS ; INDUCED ACTIVATION ; OVER-EXPRESSION ; ID1 EXPRESSION ; IN-VITRO ; CARCINOMA ; ID-1
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000282683000078
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278745]
专题	药理学第三研究室
通讯作者	Ding, Kan
作者单位	1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Glycochem & Glycobiol Lab, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci & Infinitus, Joint Lab Res Chinese Herbal Polysaccharides, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Qiu, Hong,Yang, Bo,Pei, Zhi-Chao,et al. WSS25 Inhibits Growth of Xenografted Hepatocellular Cancer Cells in Nude Mice by Disrupting Angiogenesis via Blocking Bone Morphogenetic Protein (BMP)/Smad/Id1 Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(42):32638-32646.
APA	Qiu, Hong,Yang, Bo,Pei, Zhi-Chao,Zhang, Zhang,&Ding, Kan.(2010).WSS25 Inhibits Growth of Xenografted Hepatocellular Cancer Cells in Nude Mice by Disrupting Angiogenesis via Blocking Bone Morphogenetic Protein (BMP)/Smad/Id1 Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY,285(42),32638-32646.
MLA	Qiu, Hong,et al."WSS25 Inhibits Growth of Xenografted Hepatocellular Cancer Cells in Nude Mice by Disrupting Angiogenesis via Blocking Bone Morphogenetic Protein (BMP)/Smad/Id1 Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY 285.42(2010):32638-32646.