Antiproliferative effects of interferonγ in combination withα-difluoromethylornithine on human carcinoma cell cultures

The antiproliferative effects of human recombinant interferon γ (IFNγ) in combination with α-difluoromethylornithine (DFMO) or as single agents were assessed on human cell cultures derived from carcinomas of the breast (MCF-7), the ovary (EFO-27) or the kidneys (EGI-4). Results were obtained in proliferation assays by direct cell counting. The cell lines differed considerably in their sensitivities to the antiproliferative effect of IFNγ as compared by the 50% inhibition doses of the growth (ID50). In contrast to the findings with IFNγ, similar antiproliferative effects resulted from the application of comparable doses of DFMO. While IFNγ induced cytotoxic effects in EGI-4 cells, DFMO produced only cytostatic actions in the cell lines analyzed. Synergistic growth inhibition resulted from the combined application of IFNγ and DFMO in EFO-27 cell cultures. This finding was most pronounced after treatment with IFNγ or DFMO doses below the respective ID50 values. However, antagonistic effects occurred in cells of the line EGI-4 after DFMO had been combined with IFNγ at concentrations below the cytotoxic dose range. Within the sensitivity of our proliferation assay, no synergistic interactions were found in MCF-7 cell cultures. In the cell lines tested, no relation between the sensitivity for the single agents and the effectivity of the drug combination was identified. Despite promising synergistic effects in the moderately IFNγ-sensitive ovarian carcinoma cell line EFO-27, the efficacy of the IFNγ/DFMO combination was restrained by possible antagonistic effects as demonstrated in the highly IFNγ-sensitive EGI-4 renal carcinoma cell cultures. We conclude that the differential interaction patterns in the cell cultures analyzed preclude general suggestions for clinical studies using IFNγ and DFMO.