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

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.