ID | 31598 |
JaLCDOI | |
フルテキストURL | |
著者 |
Kiura, Katsuyuki
Second Department of Medicine, Okayama University Medical School
ORCID
Kaken ID
publons
researchmap
Ohnoshi, Taisuke
Second Department of Medicine, Okayama University Medical School
Tabata, Masahiro
Second Department of Medicine, Okayama University Medical School
Kaken ID
researchmap
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
|
出版物タイトル |
Acta Medica Okayama
|
発行日 | 1993-06
|
巻 | 47巻
|
号 | 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 |
英語
|
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 Science KeyUT | |
関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/6296
|