Reduced drug accumulation in a newly established human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II).
A human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II) (CDDP), designated PC10-B3, has been established from the original cell line PC10 by a stepwise increment of the CDDP concentration. This is the first report, to our knowledge, to establish a CDDP-resistant lung squamous-carcinoma cell line. PC10-B3 has continued to proliferate in the presence of 0.5 micrograms/mL CDDP, whereas PC10 could not survive. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that PC10-B3 was 11.4-fold more resistant to CDDP than PC10 and cross-resistant to diammine(1,1-cyclobutanecarboxylate)platinum(II) (CBDCA) and 254-S, but not to doxorubicin or etoposide. PC10-B3 was characterized by a smaller DNA index and a larger cell size compared to PC10. The level of intracellular platinum accumulation was reduced by about 5- to 8-fold in PC10-B3 when compared with PC10, suggesting that reduced drug accumulation may be one of the important factors in contributing to CDDP resistance in PC10-B3.
Katabami
M
M
Laboratory of Molecular Genetics Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Fijita
H
H
Haneda
H
H
Akita
H
H
Kuzumaki
N
N
Miyamoto
H
H
Kawakami
Y
Y
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000737:chemistry / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D010984:Platinum / Q000032:analysis; D013778:Tetrazolium Salts; D013844:Thiazoles
D013778:Tetrazolium Salts; D013844:Thiazoles; D010984:Platinum; C022616:thiazolyl blue; D002945:Cisplatin