Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase

doi:10.1158/1078-0432.CCR-17-0242

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

	Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase
	Dai, Xiaoyang 5,6; Yan, Juan 1,5; Fu, Xuhong 5; Pan, Qiuming 5; Sun, Danni 5; Xu, Yuan 2; Wang, Jiang3 ; Nie, Litong 4; Tong, Linjiang 5; Shen, Aijun5
刊名	CLINICAL CANCER RESEARCH
	2017-10-15
卷号	23 期号:20 页码:6267-6278
ISSN号	1078-0432
DOI	10.1158/1078-0432.CCR-17-0242
文献子类	Article
英文摘要	Purpose: Recent epidemiological and clinical studies have suggested the benefit of aspirin for patients with cancer, which inspired increasing efforts to demonstrate the anticancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anticancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anticancer of aspirin. Experimental Design: A homogeneous time-resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay, and molecular docking were performed to identify heparanase as an aspirin-binding protein. Transwell, rat aortic rings, and chicken chorioallantoic membrane model were used to evaluate the antimetastasis and anti-angiogenesis effects of aspirin, and these phenotypes were tested in a B16F10 metastatic model, MDA-MB-231 metastatic model, and MDA-MB-435 xenograft model. Results: This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis, and growth in heparanase-dependent manner. Conclusions: In summary, this study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anticancer effects, and offers a direction for the development of small-molecule inhibitors of heparanase. (C)2017 AACR.
资助项目	"Personalized Medicines-Molecular Signature-based Drug Discovery and Development," Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; NSFC-Shandong Joint Fund for Marine Science Research Centers[U1406402] ; Natural Science Foundation of China[81302791] ; Youth Innovation Promotion Association CAS[00000000] ; Shanghai Talent Development Funds[201663] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020326]
WOS关键词	NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; COLORECTAL-CANCER ; BREAST-CANCER ; COLON-CANCER ; INDUCED APOPTOSIS ; GROWTH-FACTOR ; CELLS ; RISK ; SULFATE ; SUPPRESSES
WOS研究方向	Oncology
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000413151000027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272447]
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	Huang, Xun; Ding, Jian; Geng, Meiyu
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China; 6.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Dai, Xiaoyang,Yan, Juan,Fu, Xuhong,et al. Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase[J]. CLINICAL CANCER RESEARCH,2017,23(20):6267-6278.
APA	Dai, Xiaoyang.,Yan, Juan.,Fu, Xuhong.,Pan, Qiuming.,Sun, Danni.,...&Geng, Meiyu.(2017).Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase.CLINICAL CANCER RESEARCH,23(20),6267-6278.
MLA	Dai, Xiaoyang,et al."Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase".CLINICAL CANCER RESEARCH 23.20(2017):6267-6278.