Reduced drug accumulation in a newly established human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II)

Biochem Pharmacol. 1992 Jul 22;44(2):394-7. doi: 10.1016/0006-2952(92)90027-g.

Abstract

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.

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Division / drug effects
  • Cell Line / chemistry
  • Cell Line / metabolism
  • Cisplatin / metabolism*
  • Cisplatin / pharmacology
  • Drug Resistance / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Platinum / analysis
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Tetrazolium Salts
  • Thiazoles
  • Platinum
  • thiazolyl blue
  • Cisplatin