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ID 31598
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Author
Ohnoshi, Taisuke
Tabata, Masahiro Kaken ID researchmap
Shibayama, Takuo
Kimura, Ikuro
Abstract
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.
Keywords
Adriamycin-resistant cell line
MDR1 mRNA
glutathione
glutathione S-transferasse π
DNA topoisomerase II
Amo Type
Article
Published Date
1993-06
Publication Title
Acta Medica Okayama
Volume
volume47
Issue
issue3
Publisher
Okayama University Medical School
Start Page
191
End Page
197
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
Copyright © 1999 Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Science KeyUT
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/6296