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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-10-15
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0386-300X
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Establishment of an adriamycin-resistant subline of human small cell lung cancer showing multifactorial mechanisms of resistance.
pubmed:affiliation
Second Department of Medicine, Okayama University Medical School, Japan.
pubmed:publicationType
Journal Article