國家衛生研究院 NHRI:Item 3990099045/9347
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    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/9347


    题名: The novel VEGF121-VEGF165 fusion attenuates angiogenesis and drug resistance via targeting VEGFR2-HIF-1alpha-VEGF165/Lon signaling through PI3K-AKT-mTOR pathway
    其它题名: The novel VEGF121-VEGF165 fusion attenuates angiogenesis and drug resistance via targeting VEGFR2-HIF-1α-VEGF165/Lon signaling through PI3K-AKT-mTOR pathway
    作者: Tsai, JL;Lee, YM;Pan, CY;Lee, AYL
    贡献者: National Institute of Cancer Research
    摘要: Anti-angiogenesis therapy is one major approach of cancer therapies nowadays. Unfortunately, anti-angiogenesis therapy targeting VEGF-A was recently stumbled by the drug-resistance that results from adaptive mechanisms, such as intratumor hypoxia. To obtain a more efficient therapeutic response, we created and identified a novel chimeric fusion of VEGF121 and VEGF165, which was connected by Fc region of human IgG1 to enhance dimerization. We found that the treatment of VEGF121-VEGF165 chimeric protein reduces proliferation, migration, invasion, and tube formation in endothelial and/or cancer cells through competing VEGF165 homodimer in a paracrine and an autocrine manner. Furthermore, the fusion protein attenuated autocrine VEGFR2-HIF-1alpha-VEGF165/Lon signaling through PI3K-AKT-mTOR pathway in cancer cells. In conclusion, our data demonstrated that the chimeric VEGF121-VEGF165 arrests the tube formation of endothelial cells and interferes with tumor cell growth, migration and invasion, suggesting that it could be a potential drug as an angiogenesis antagonist in cancer therapy. The VEGF121-VEGF165 targets not only paracrine angiogenic cascade of endothelial cells but also autocrine PI3K-AKT-mTOR-mediated VEGFR2-HIF-1alpha-VEGF165/Lon signaling that drives drug resistance in tumor cells. Our study will open up the patient opportunities to combat drug resistance to antiangiogenic therapy.
    日期: 2016-01
    關聯: Current Cancer Drug Targets. 2016 Jan;6(3):275-286.
    Link to: http://dx.doi.org/10.2174/156800961603160206125352
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1568-0096&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000373449300008
    显示于类别:[李岳倫] 期刊論文

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