國家衛生研究院 NHRI:Item 3990099045/10712
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 857699      線上人數 : 751
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/3990099045/10712


    題名: Specificity protein 1-modulated superoxide dismutase 2 enhances temozolomide resistance in glioblastoma, which is independent of O6-methylguanine-DNA methyltransferase
    作者: Chang, KY;Hsu, TI;Hsu, CC;Tsai, SY;Liu, JJ;Chou, SW;Liu, MS;Liou, JP;Ko, CY;Chen, KY;Hung, JJ;Chang, WC;Chuang, CK;Kao, TJ;Chuang, JY
    貢獻者: National Institute of Cancer Research
    摘要: Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants derived from MGMT-negative GBM clinical samples and cell lines were studied, revealing there to be increased specificity protein 1 (Sp1) expression associated with reduced reactive oxygen species (ROS) accumulation following TMZ treatment. Analysis of gene expression databases along with cell studies identified the ROS scavenger superoxide dismutase 2 (SOD2) as being disease-related. SOD2 expression was also increased, and it was found to be co-expressed with Sp1 in TMZ-resistant cells. Investigation of the SOD2 promoter revealed Sp1 as a critical transcriptional activator that enhances SOD2 gene expression. Co-treatment with an Sp1 inhibitor restored the inhibitory effects of TMZ, and decreased SOD2 levels in TMZ-resistant cells. This treatment strategy restored susceptibility to TMZ in xenograft animals, leading to prolonged survival in an orthotopic model. Thus, our results suggest that Sp1 modulates ROS scavengers as a novel mechanism to increase cancer malignancy and resistance to chemotherapy. Inhibition of this pathway may represent a potential therapeutic target for restoring treatment susceptibility in GBM.
    日期: 2017-08-12
    關聯: Redox Biology. 2017 Aug 12;13:655-664.
    Link to: http://dx.doi.org/10.1016/j.redox.2017.08.005
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2213-2317&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000410470000060
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85027521843
    顯示於類別:[張光裕] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    PUB28822335.pdf2217KbAdobe PDF581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