Bando T, Kasahara K, Shibata K, Nakatsumi Y, Fujimura M, Matsuda T
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Anticancer Res. 1994 Nov-Dec;14(6B):2727-30.
Recently, the importance of the potassium pump in the cellular accumulation of cis-diamminedichloroplatinum(II) (CDDP) has been reported. In this study we evaluated the role of the proton pump as a determinant of the sensitivity to CDDP in non-small cell lung cancer cell lines in vitro by using a selective proton pump inhibitor, AG-2000. PC-9 and PC-9/CDDP cell lines, which are sensitive or resistant to CDDP, were used for these experiments. PC-9/CDDP was 17.4-fold more resistant to CDDP than PC-9 cells. Relative resistance was not altered by co-incubation with a non-cytotoxic dosage of AG-2000. From these studies, it was shown that the proton pump inhibitor AG-2000 did not enhance the sensitivity to CDDP. However, as AG-2000 is not cytotoxic and does not compromise the CDDP-sensitivity in NSCLC cells at the concentration of clinical use for gastroduodenal ulcer, AG-2000 can be used with CDDP in chemotherapy for lung cancer.
最近，有报道称钾泵在顺二氯二氨合铂（II）（CDDP）的细胞蓄积中具有重要作用。在本研究中，我们通过使用选择性质子泵抑制剂AG - 2000，在体外评估了质子泵作为非小细胞肺癌细胞系对CDDP敏感性决定因素的作用。对CDDP敏感或耐药的PC - 9和PC - 9/CDDP细胞系用于这些实验。PC - 9/CDDP对CDDP的耐药性比PC - 9细胞高17.4倍。与非细胞毒性剂量的AG - 2000共同孵育不会改变相对耐药性。从这些研究中可以看出，质子泵抑制剂AG - 2000不会增强对CDDP的敏感性。然而，由于AG - 2000无细胞毒性，且在用于胃十二指肠溃疡的临床使用浓度下不会损害NSCLC细胞对CDDP的敏感性，因此AG - 2000可与CDDP联合用于肺癌化疗。
