Adriamycin 耐性ヒト膀胱癌培養細胞株の樹立と耐性機序に関する研究 Establishment of an adriamycin-resistant human bladder cancer cell line (T-24/ADM) and analysis of the mechanism of resistance

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A human bladder cencer cell line resistant to adriamycin (ADM), T-24/ADM was establishied in vitro by exposing T-24 parent cells to a progressively higher concentration of the drug over an 18 month period. The T-24/ADM was 34.9 times more resistant to ADM than the T-24 parent. The T-24/ADM exhibited cross resistance to ADM derivatives, vinca alkaloid (vindesine, vincristine), etoposide and SN-38, but collateral sensitivity to methotrexate. The biological and biochemical characteristics of T-24/ADM were examined in terms of ADM-resistance.Although a flow cytometric analysis showed that Pglycoprotein is not expressed on the T-24/ADM cells, lower accumalation of the drug caused by decreased uptake and increaced active efflux were observed. The cellular level of glutathione-S-transferase π was 1.8-fold higher than the parent cells and the activity of nuclear extracts of DNA topoisomerase Ⅱ for T-24/ADM assayed by decatenation of kinetoplast DNA was lower, about one-half that of the T-24 parent. Confocal laser microscopy revealed the difference in intracellular distribution of ADM in T-24/ADM; in particular, the accumlation of the drug in the nucleus decreased. Additionally western blot analysis showed an enhanced expression of multidrug resistance-associated protein (MRP) in the T-24/ADM cells.This resistant cell may be used as an experimantal system to elucidate the mechanisum of ADM resistance and also as a model for developing new chemotherapeutic strategies against multi-drug resistant bladder cancer.

収録刊行物

  • 岡山醫學會雜誌

    岡山醫學會雜誌 113(1), 1-16, 2001-04-28

    岡山医学会

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各種コード

  • NII論文ID(NAID)
    10012336220
  • NII書誌ID(NCID)
    AN00032489
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    00301558
  • データ提供元
    CJP書誌  IR 
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