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