Bando T, Fujimura M, Kasahara K, Matsuda T
Third Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Anticancer Res. 1998 Mar-Apr;18(2A):1085-9.
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.
顺二氯二氨铂（II）（CDDP）是最有效的抗癌药物。据报道，CDDP的细胞内蓄积是决定其耐药性的重要步骤，这可能受Na⁺、K⁺-ATP酶活性调节。在本研究中，使用人肺癌细胞系评估了膜Na⁺、K⁺-ATP酶活性在CDDP细胞内蓄积中的意义。Na⁺、K⁺-ATP酶在每个细胞系中均有活性，不仅在非小细胞肺癌（NSCLC）细胞系中，在小细胞肺癌（SCLC）细胞系中也有活性。在NSCLC细胞系中，Na⁺、K⁺-ATP酶活性与CDDP的细胞内蓄积之间存在显著相关性，并且在每个细胞系中，Na⁺、K⁺-ATP酶抑制剂哇巴因可使蓄积显著降低。然而，在对CDDP敏感性优于NSCLC细胞系的SCLC细胞系中，酶活性与CDDP细胞内蓄积之间的相关性不显著。这些结果表明，Na⁺、K⁺-ATP酶在NSCLC和SCLC细胞中均有活性，然而，该酶作为CDDP主动转运体的重要性可能仅限于NSCLC细胞。细胞内蓄积机制作为SCLC细胞对CDDP敏感性的决定因素可能不那么重要。
