Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cis-Diamminedichloroplatinum(II) (CDDP) is a key anticancer agent. It has been reported that intracellular accumulation of CDDP is an important step as a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase activity. In this study, the significance of membrane Na+, K(+)-ATPase activity and the role of thromboxane (TX) receptors were evaluated using human lung cancer cell lines. In the non-small-cell lung cancer (NSCLC) cell line, EBC-1, sensitivity to CDDP was improved by treatment with two different selective thromboxane receptor antagonists, calcium 5(z)-[1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo [2.2.1]hept-2-yl]-5-heptenoate hydrate (S-1452), and (3R)-3-(4-fluorophenyl sulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropanoic acid (BAYu3405). Na+, K(+)-ATPase was activated and intracellular accumulation of CDDP increased with treatment in EBC-1. In the small-cell lung cancer (SCLC) cell lines, SBC-1, sensitivity to CDDP and Na+, K(+)-ATPase activity did not change significantly, and intracellular accumulation of CDDP was not modulated. These results suggest the importance of the TX receptors as determinants of the sensitivity to CDDP in NSCLC cell lines. However, Na+, K(+)-ATPase activity and the role of TX receptors may not be so significant in the resistance mechanisms to CDDP in SCLC cell lines. In EBC-1 cells, the specific binding of S-145 was evident, but not in SBC-1 cells. The difference in TX receptors in NSCLC and SCLC cell lines may be one of the reasons for the variety of the antitumor effects of CDDP in chemotherapy for lung cancer.
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PMID:Role of thromboxane receptor on the intracellular accumulation of cis-diamminedichloroplatinum(II) in non-small-cell but not in small-cell lung cancer cell lines. 961 69

cis-Diamminedichloroplatinum(II) (CDDP) is the most active anticancer agent. It has been reported that intracellular accumulation of CDDP is an important step as a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase activity. In this study, the significance of membrane Na+, K(+)-ATPase activity in the intracellular accumulation of CDDP were evaluated using human lung cancer cell lines. Na+, K(+)-ATPase was active in each cell line, not only non-small-cell lung cancer (NSCLC) but also in small-cell lung cancer (SCLC) cell lines. In NSCLC cell lines, there were significant correlations between Na+, K(+)-ATPase activities and intracellular accumulation of CDDP and the accumulation significantly decreased by ouabain, an inhibitor of Na+, K(+)-ATPase in each cell line. However, the correlation between enzyme activity and intracellular accumulation of CDDP were not significant in SCLC cell lines where sensitivity to CDDP was better than in NSCLC cell lines. These results suggest Na+, K(+)-ATPase are active in both NSCLC and SCLC cells, however, the importance of the enzyme as an active transporter of CDDP may be limited only to NSCLC cells. The mechanisms of intracellular accumulation may not be so important as a determinant of sensitivity to CDDP in SCLC cells.
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PMID:Significance of Na+, K(+)-ATPase on intracellular accumulation of cis-diamminedichloroplatinum(II) in human non-small-cell but not in small-cell lung cancer cell lines. 961 70