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

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Abstract
Human ovarian carcinoma cells (2008 and its cisplatin‐resistant sub‐line 2008/C13*) were sensitized to cisplatin by treatment with human recombinant gamma interferon (IFNγ). IFNγ produced no significant change in the uptake of CDDP. Exposure of 2008 and 2008/C13* cells to IFNγ resulted in a time‐dependent decrease of cellular glutathione and total glutathione‐S‐transferase activity, principally the π isoform. By contrast, the treatment of 2008 and 2008/C13* cell lines with IFNγ induced rather than suppressed metallothionein IIA mRNA levels. IFNγ 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 IFNγ, and this decrease was dose‐dependent. Our results indicate that the mechanism of IFNγ‐induced sensitization in human ovarian‐cancer cell lines is multifactorial. © 1995 Wiley‐Liss, Inc.