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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1994-5-6
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pubmed:abstractText |
We have reported that the cellular uptake of cis-diamminedichloroplatinum(II) (CDDP) was inhibited by an Na+,K(+)-adenosine triphosphatase (ATPase) inhibitor, ouabain, in a human non-small-cell lung-cancer cell line, PC-14, but not in its CDDP-resistant cell line, PC-14/CDDP. [3H]Ouabain binding of PC-14/CDDP was about 50% lower than that of PC-14. Accordingly, we speculated that a decrease in Na+,K(+)-ATPase activity in PC-14/CDDP might contribute to the decrease in cellular CDDP accumulation. To clarify the relationship between the activity or expression of Na+,K(+)-ATPase and cellular CDDP accumulation, we established an ouabain-resistant non-small-cell lung-cancer cell line (PC-14/OB300), which showed 1.9-fold resistance to the cytotoxicity of ouabain. Interestingly, this cell line was 4.2-fold more sensitive to CDDP than PC-14. The accumulation of CDDP in PC-14/OB300 was increased to 2.7-fold that in PC-14. This elevation of CDDP accumulation was not considered to be caused by increased passive diffusion, because the accumulation of CDDP in PC-14/OB300 was also inhibited by ouabain compared to PC-14. As one of the indices of Na+,K(+)-ATPase activity, we determined cellular 86Rb+ influx rates. The 86Rb+ influx rate was 1.5-fold higher in PC-14/OB300 and fell to 0.7-fold in PC-14/CDDP compared with PC-14. The mRNA expression of Na+,K(+)-ATPase was increased in PC-14/OB300 and decreased in PC-14/CDDP. There was no difference in cellular [3H]ouabain binding between PC-14/OB300 and PC-14. It is possible that Na+,K(+)-ATPase of PC-14/OB300 has a different affinity for ouabain from that of PC-14. Our results suggest that the enzyme activity or the level of expression of Na+,K(+)-ATPase may contribute to the cellular uptake of CDDP and determine the sensitivity to CDDP.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Ouabain,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Rubidium,
http://linkedlifedata.com/resource/pubmed/chemical/Rubidium Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
57
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
111-6
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8150528-Adenocarcinoma,
pubmed-meshheading:8150528-Blotting, Northern,
pubmed-meshheading:8150528-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:8150528-Cisplatin,
pubmed-meshheading:8150528-Drug Resistance,
pubmed-meshheading:8150528-Drug Screening Assays, Antitumor,
pubmed-meshheading:8150528-Humans,
pubmed-meshheading:8150528-Lung Neoplasms,
pubmed-meshheading:8150528-Ouabain,
pubmed-meshheading:8150528-RNA, Messenger,
pubmed-meshheading:8150528-Rubidium,
pubmed-meshheading:8150528-Rubidium Radioisotopes,
pubmed-meshheading:8150528-Sodium-Potassium-Exchanging ATPase,
pubmed-meshheading:8150528-Tumor Cells, Cultured
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pubmed:year |
1994
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pubmed:articleTitle |
Ouabain-resistant non-small-cell lung-cancer cell line shows collateral sensitivity to cis-diamminedichloroplatinum(II) (CDDP).
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pubmed:affiliation |
Pharmacology Division of National Cancer Center Research Institute, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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