國家衛生研究院 NHRI:Item 3990099045/7528
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 861825      線上人數 : 806
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/7528


    題名: Attenuation of argininosuccinate lyase inhibits cancer growth via cyclin A2 and nitric oxide
    作者: Huang, HL;Hsu, HP;Shieh, SC;Chang, YS;Chen, WC;Cho, CY;Teng, CF;Su, IJ;Hung, WC;Lai, MD
    貢獻者: Division of Infectious Diseases;National Institute of Cancer Research
    摘要: Arginine biosynthesis and nitric oxide (NO) production are important for cancer homeostasis. Degradation of arginine may be employed to inhibit liver tumors with low argininosuccinate synthetase expression. In this report, we investigated an alternative therapeutic approach by targeting argininosuccinate lyase (ASL). ASL is transcriptionally induced by endoplasmic reticulum stress and is overexpressed in some human liver tumors. Knockdown of ASL expression by shRNA in three liver cancer cell lines, ML-1, HuH-7, and HepG2, decreased colony formation in vitro and tumor growth in vivo. Furthermore, lentiviral infection of ASL shRNA inhibited tumor growth in a therapeutic animal tumor model. Analysis of ASL shRNA on the cell cycle progression revealed a G2/M delay. Among cell-cycle regulatory molecules, cyclin A2 expression was reduced. Reintroduction of exogenous cyclin A2 restored the cell growth in ASL-knockdown cells. Autophagy was observed in the cells treated with ASL shRNA, as demonstrated by an increase in LC3-II levels and autophagosome formation. The total cellular arginine level was not altered significantly. Inhibition of autophagy further attenuated cell growth, suggesting that autophagy induced by ASL shRNA plays a feedback pro-survival function. Knockdown of ASL reduced NO content, and addition of NO donor partially recovered the growth inhibition by ASL shRNA. In summary, downregulation of ASL attenuated tumor growth and the inhibition was mainly mediated by a decrease of cyclin A2 and NO.
    日期: 2013-11
    關聯: Molecular Cancer Therapeutics. 2013 Nov;12(11):2505-2516.
    Link to: http://dx.doi.org/10.1158/1535-7163.mct-12-0863
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-7163&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000326886000020
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84887455091
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文
    [洪文俊] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    PB2013100701.pdf2738KbAdobe PDF460檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋