Mechanism of interaction between cisplatin and human recombinant interferon gamma in human ovarian-cancer cell lines

Int J Cancer. 1995 May 29;61(5):643-8. doi: 10.1002/ijc.2910610510.


Human ovarian carcinoma cells (2008 and its cisplatin-resistant sub-line 2008/C13*) were sensitized to cisplatin by treatment with human recombinant gamma interferon (IFN gamma). IFN gamma produced no significant change in the uptake of CDDP. Exposure of 2008 and 2008/C13* cells to IFN gamma resulted in a time-dependent decrease of cellular glutathione and total glutathione-S-transferase activity, principally the pi isoform. By contrast, the treatment of 2008 and 2008/C13* cell lines with IFN gamma induced rather than suppressed metallothionein IIA mRNA levels. IFN gamma changed neither the formation of total platinum-DNA adducts, nor DNA repair. A significant decrease in c-erbB-2 expression was observed both in sensitive and in resistant cell lines after treatment with IFN gamma, and this decrease was dose-dependent. Our results indicate that the mechanism of IFN gamma-induced sensitization in human ovarian-cancer cell lines is multifactorial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cisplatin / metabolism
  • Cisplatin / pharmacology*
  • DNA Damage
  • DNA Repair
  • Female
  • Gene Expression
  • Genes, erbB-2 / genetics
  • Humans
  • Interferon-gamma / pharmacology*
  • Metallothionein / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • RNA, Messenger / analysis
  • Recombinant Proteins
  • Tumor Cells, Cultured


  • RNA, Messenger
  • Recombinant Proteins
  • Interferon-gamma
  • Metallothionein
  • Cisplatin