國家衛生研究院 NHRI:Item 3990099045/2733
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 858362      線上人數 : 500
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/3990099045/2733


    題名: Combined modalities of resistance in an oxaliplatin-resistant human gastric cancer cell line with enhanced sensitivity to 5-fluorouracil
    作者: Chen, CC;Chen, LT;Tsou, TC;Pan, WY;Kuo, CC;Liu, JF;Yeh, SC;Tsai, FY;Hsieh, HP;Chang, JY
    貢獻者: National Institute of Cancer Research;Division of Biotechnology and Pharmaceutical Research;Division of Environmental Health and Occupational Medicine
    摘要: To identify mechanisms underlying oxaliplatin resistance, a subline of the human gastric adenocarcinoma TSGH cell line, S3, was made resistant to oxaliplatin by continuous selection against increasing drug concentrations. Compared with the parental TSGH cells, the S3 subline showed 58- fold resistance to oxaliplatin; it also displayed 11-, 2-, and 4.7- fold resistance to cis- diammine- dichloroplatinum ( II) ( CDDP), copper sulphate, and arsenic trioxide, respectively. Interestingly, S3 cells were fourfold more susceptible to 5- fluorouracilinduced cytotoxicity due to downregulation of thymidylate synthase. Despite elevated glutathione levels in S3 cells, there was no alteration of resistant phenotype to oxaliplatin or CDDP when cells were co- treated with glutathione- depleting agent, l- buthionine( S, R)- sulphoximine. Cellular CDDP and oxaliplatin accumulation was decreased in S3 cells. In addition, amounts of oxaliplatin- and CDDP - DNA adducts in S3 cells were about 15 and 40% of those seen with TSGH cells, respectively. Western blot analysis showed increased the expression level of copper transporter ATP7A in S3 cells compared with TSGH cells. Partial reversal of the resistance of S3 cells to oxaliplatin and CDDP was observed by treating cell with ATP7A- targeted siRNA oligonucleotides or P- type ATPaseinhibitor sodium orthovanadate. Besides, host reactivation assay revealed enhanced repair of oxaliplatin- or CDDP- damaged DNA in S3 cells compared with TSGH cells. Together, our results show that the mechanism responsible for oxaliplatin and CDDP resistance in S3 cells is the combination of increased DNA repair and overexpression of ATP7A. Downregulation of thymidylate synthase in S3 cells renders them more susceptible to 5- fluorouracil- induced cytotoxicity. These findings could pave ways for future efforts to overcome oxaliplatin resistance.
    關鍵詞: Oncology
    日期: 2007-07-31
    關聯: British Journal of Cancer. 2007 Jul;97(3):334-344.
    Link to: http://dx.doi.org/10.1038/sj.bjc.6603866
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-0920&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000248444900010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34547590004
    顯示於類別:[張俊彥] 期刊論文
    [謝興邦] 期刊論文
    [鄒粹軍] 期刊論文
    [郭靜娟] 期刊論文
    [陳立宗] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    000248444900010.pdf246KbAdobe PDF853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