The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo
文献类型：期刊论文
| 作者 | Ma, Jingui; Xin, Xianliang; Meng, Linghua ; Tong, Linjiang; Lin, Liping; Geng, Meiyu; Ding, Jian
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| 刊名 | PLOS ONE
 |
| 出版日期 | 2008-11-20 |
| 卷号 | 3期号:11 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0003774 |
| 文献子类 | Article |
| 英文摘要 | Despite the emerging success of multi-targeted protein tyrosine kinase (PTK) inhibitors in cancer therapy, significant side effects and resistance concerns seems to be avoided unlikely. The aim of the present study was to identify novel multi-targeting PTK inhibitors. The kinase enzymatic activities were measured by enzyme-linked immunosorbent assay (ELISA). The antiproliferative activities in human microvascular endothelial cells (HMECs) were evaluated by sulforhodamine (SRB) assay. The phosphorylation of kinases and their downstream molecules was probed by western blot analysis. The binding mode between MdOS and PTKs was profiled by surface plasmon resonance (SPR) approach and molecular simulation. Tube formation assay, rat aortic ring method and chicken chorioallantoic membrane assay were combined to illustrate the in vitro and in vivo anti-angiogenic effects. Results indicated that MdOS, a novel marine-derived oligosaccharide sulfate, exhibited a broad-spectrum PTK inhibitory action. At an enzymatic level, MdOS inhibited HER2, EGFR, VEGFR, PDGFR, c-Kit, FGFR1 and c-Src, with little impact on FGFR2. In cellular settings, MdOS inhibited phosphorylation of PTKs, exemplified by HER2, EGFR and VEGFR2, and downstream molecules of Erk1/2 and AKT. Further studies demonstrated that MdOS acted as an ATP-competitive inhibitor via directly binding to the residues of entrance rather than those of the ATP-binding pocket. Furthermore, MdOS inhibited proliferation and tube formation of HMECs, arrested microvessel outgrowth of rat aortic rings and hindered the neovascularization of chick allantoic membrane. Taken together, results presented here indicated that MdOS exhibited anti-angiogenic activity in a PTK-dependent manner and make it a promising agent for further evaluation in PTK-associated cancer therapy. |
| 资助项目 | Science Foundation of China[00000000] ; Natural Science Foundation of China[30725046] ; Natural Science Foundation of China[30721005] ; Knowledge Innovation Program of Chinese Academy of Sciences[KSCX2-YW-R-25] ; Science and Technology Commission of Shanghai[07dz05906] ; National Basic Research Program[2003CB716400] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000265448600007 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279430]  |
| 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 | Ma, Jingui |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Div Antitumor Pharmacol,State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Jingui,Xin, Xianliang,Meng, Linghua,et al. The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo[J]. PLOS ONE,2008,3(11). |
| APA | Ma, Jingui.,Xin, Xianliang.,Meng, Linghua.,Tong, Linjiang.,Lin, Liping.,...&Ding, Jian.(2008).The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo.PLOS ONE,3(11). |
| MLA | Ma, Jingui,et al."The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo".PLOS ONE 3.11(2008). |
入库方式： OAI收割
来源：上海药物研究所
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