Ouabain-resistant non-small-cell lung-cancer CELL LINE SHOWS COLLATERAL SENSITIVITY TO cis-diamminedichloroplatinum(II) (CDDP)
✍ Scribed by Tohru Ohmori; Kazuto Nishio; Sei Ohta; Naohiro Kubota; Mitsuru Adachi; Kazuhide Komiya; Nagahiro Saijo
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 768 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We have reported that the cellular uptake of cis-diamminedichloroplatinum(ll) (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-I4/CDDP. ['HIOuabain binding of PC-I4/CDDP was about 50% lower than that of PC-14. Accordingly, we speculated that a decrease in Na',K+-ATPase activity in PC-I4/CDDP might contribute t o 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-smallcell lung-cancer cell line (PC-14/06300), which showed I .Cfold resistance t o the cytotoxicity of ouabain. Interestingly, this cell line was 4.2-fold more sensitive t o CDDP than PC-14. The accumulation of CDDP in PC-l4/08300 was increased t o 2.7-fold that in PC-14. This elevation of CDDP accumulation was not considered t o be caused by increased passive diffusion, because the accumulation of CDDP in PC-I4/06300 was also inhibited by ouabain compared t o PC-14. As one of the indices of Na*,K*-ATPase activity, we determined cellular 86Rb+ influx rates. The Wb* influx rate was I .S-fold higher in PC-I4/08300 and fell t o 0.7-fold in PC-I4/CDDP compared with PC-14. The mRNA expression of Na',K'-ATPase was increased in PC-14/ 06300 and decreased in PC-I4/CDDP. There was no difference in cellular [3H]ouabain binding between PC-14/06300 and PC-14. It is possible that Na',K'-ATPase of PC-I4/08300 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 t o the cellular uptake of CDDP and determine the sensitivity t o CDDP.