Switch to
Predicate | Object |
---|---|
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 |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
|
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-meshheading:8104372-Carcinoma, Small Cell,
pubmed-meshheading:8104372-Carrier Proteins,
pubmed-meshheading:8104372-DNA Topoisomerases, Type II,
pubmed-meshheading:8104372-Doxorubicin,
pubmed-meshheading:8104372-Drug Resistance,
pubmed-meshheading:8104372-Glutathione,
pubmed-meshheading:8104372-Glutathione Transferase,
pubmed-meshheading:8104372-Humans,
pubmed-meshheading:8104372-Lung Neoplasms,
pubmed-meshheading:8104372-Membrane Glycoproteins,
pubmed-meshheading:8104372-Neoplasm Proteins,
pubmed-meshheading:8104372-P-Glycoprotein,
pubmed-meshheading:8104372-RNA, Messenger,
pubmed-meshheading:8104372-Tumor Cells, Cultured
|
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
|