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ID 31598
JaLCDOI
フルテキストURL
著者
Kiura, Katsuyuki Second Department of Medicine, Okayama University Medical School
Ohnoshi, Taisuke Second Department of Medicine, Okayama University Medical School
Tabata, Masahiro Second Department of Medicine, Okayama University Medical School
Shibayama, Takuo Second Department of Medicine, Okayama University Medical School
Kimura, Ikuro Second Department of Medicine, Okayama University Medical School
抄録
A subline highly resistant to Adriamycin (SBC-3/ADM100) was isolated in vitro from the human small cell lung cancer cell line, SBC-3, by culturing in progressively higher concentrations of Adriamycin. The SBC-3/ADM100 cells were 106-fold more resistant to the drug than the parent cells in an inhibitory concentration of 50% determined by the MTT assay. The population-doubling time was much longer in SBC-3/ADM100 than in the parent cells. Northern blot hybridization revealed marked overexpression of the MDR1 mRNA in the resistant cells. P-glycoprotein overexpression and a decrease in intracellular accumulation of Adriamycin were demonstrated in SBC-3/ADM100, indicating that outward drug transport was the major mechanism of resistance in this subline. Additionally, a significant elevation of the intracellular glutathione content coupled with the glutathione S-transferase (GST) pi level and a decrease in DNA topoisomerase II (Topo II) activity were noted in this resistant subline. These results indicate that the mechanism of resistance to Adriamycin is multifactorial; involving altered growth characteristics, an enhanced outward transport, enhanced drug detoxification process, and decreased target enzyme activity. The resistant subline will serve as a useful tool in the search for ways to overcome drug resistance.
キーワード
Adriamycin-resistant cell line
MDR1 mRNA
glutathione
glutathione S-transferasse π
DNA topoisomerase II
Amo Type
Article
発行日
1993-06
出版物タイトル
Acta Medica Okayama
47巻
3号
出版者
Okayama University Medical School
開始ページ
191
終了ページ
197
ISSN
0386-300X
NCID
AA00508441
資料タイプ
学術雑誌論文
言語
English
著作権者
Copyright © 1999 Okayama University Medical School
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Sience KeyUT
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/6296