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学科主题: 药学
题名:
ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase-dependent Matrix Metalloproteinase Pathway
作者: Zeng, Ke-Wu1; Song, Fang-Jiao2; Li, Ning1; Dong, Xin1; Jiang, Yong1; Tu, Peng-Fei1
刊名: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
发表日期: 2015-02-01
DOI: 10.1111/bcpt.12305
卷: 116, 期:2, 页:115-123
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: FIBROBLAST-GROWTH-FACTOR ; VEIN ENDOTHELIAL-CELLS ; SMOOTH-MUSCLE-CELLS ; THERAPEUTIC IMPLICATIONS ; TUMOR ANGIOGENESIS ; ANTI-ANGIOGENESIS ; DRUG DISCOVERY ; CANCER-THERAPY ; LUNG-CANCER ; IN-VITRO
英文摘要:

As angiogenesis is an important target for antitumour drugs, the agents that inhibit angiogenesis may help reduce the use of chemotherapy by blocking tumour blood supply. In this study, we investigated a potent angiogenesis inhibitor, ASC, a steroidal saponin compound, which has been purified from Ophitopogin japonicus (L.f) Ker.-Gawl. Our observations showed that ASC significantly suppressed human umbilical vein endothelial cell (HUVECs) growth both in vitro and in vivo. This may be resulted from the G2/M cell cycle arrest effects of ASC. Moreover, ASC inhibited HUVECs invasion and tube formation processes, which were associated with endothelial cells remodelling. A mechanism study indicated that ASC down-regulated the expression of Src tyrosine kinase, further leading to the blockage of Akt-dependent matrix metalloproteinases (mainly for MMP-9) signalling pathway, which was functionally associated with angiogenic blood vessels. Finally, ASC significantly inhibited angiogenesis and MMPs/VEGF expression in the subcutaneously injected matrigel in C57/BL mice. These findings suggest that ASC might be a potential drug candidate in anti-angiogenesis and anticancer therapies.

语种: 英语
所属项目编号: 2012ZX09301002-002-002 ; 81303253 ; 30873072 ; 2013T60045
项目资助者: National Key Technology R &amp ; D Programme &prime ; New Drug Innovation&prime ; of China ; Natural Science Foundation of China ; China Postdoctoral Science Foundation
WOS记录号: WOS:000348497700005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63330
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Res Studio Integrat Tradit & Western Med, Hosp 1, Beijing 100191, Peoples R China

Recommended Citation:
Zeng, Ke-Wu,Song, Fang-Jiao,Li, Ning,et al. ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase-dependent Matrix Metalloproteinase Pathway[J]. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,2015,116(2):115-123.
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