Effect of proton pump inhibitor on cell growth and sensitivity to cis-diamminedichloroplatinum(II) in non-small cell lung cancer cell lines.
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.
Bando
T
T
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Kasahara
K
K
Shibata
K
K
Nakatsumi
Y
Y
Fujimura
M
M
Matsuda
T
T
D000230:Adenocarcinoma; D001562:Benzimidazoles / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity*; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D011725:Pyridines; C058689:AG 2000; D002945:Cisplatin