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ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase-dependent Matrix Metalloproteinase Pathway
Zeng, Ke-Wu1; Song, Fang-Jiao2; Li, Ning1; Dong, Xin1; Jiang, Yong1; Tu, Peng-Fei1
刊名BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
2015-02-01
DOI10.1111/bcpt.12305
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
WOS记录号WOS:000348497700005
项目编号2012ZX09301002-002-002 ; 81303253 ; 30873072 ; 2013T60045
资助机构National Key Technology R &amp ; D Programme &prime ; New Drug Innovation&prime ; of China ; Natural Science Foundation of China ; China Postdoctoral Science Foundation
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63330
专题北京大学药学院
北京大学药学院_天然药物学系
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
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GB/T 7714
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.
APA Zeng, Ke-Wu,Song, Fang-Jiao,Li, Ning,Dong, Xin,Jiang, Yong,&Tu, Peng-Fei.(2015).ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase-dependent Matrix Metalloproteinase Pathway.BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,116(2),115-123.
MLA Zeng, Ke-Wu,et al."ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase-dependent Matrix Metalloproteinase Pathway".BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 116.2(2015):115-123.
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