Establishment of an adriamycin-resistant subline of human small cell lung cancer showing multifactorial mechanisms of resistance.

K. Kiura, T. Ohnoshi, M. Tabata, T. Shibayama, I. Kimura

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalActa medica Okayama
Volume47
Issue number3
Publication statusPublished - Jun 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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