Expression of a Resistance Mechanism in Ovarian and Cervical Carcinoma Cells Prevents Their Lysis by γ-Interferon

Despite extensive evidence that recombinant human γ-interferon (IFN-γ) exerts antiproliferative effects on a variety of cancer cell lines, IFN-γ has not been shown to lyse cells in vitro. In order to determine whether some cancer cells might actively resist lysis by IFN-γ, we examined eight arbitrarily selected cell lines derived from gynecological malignancies (ME-180, MS751, HT-3, SiHa, and C-33A human cervical carcinoma lines; Caov-3, SK-OV-3, and NIH:OVCAR-3 human ovarian carcinoma cell lines) for lysis by IFN-γ. In a 24-h assay involving release of 5,Cr from cells, none of these cell lines was lysed by IFN-γ, either alone or in combination with actinomycin-D or emetine, two inhibitors of protein synthesis. However, pretreatment of cells with 100 units/ml of IFN-γ for 24 h, followed by inhibition of protein synthesis, led to significantly increased lysis of the cell lines ME-180, MS751, and Caov-3. These results indicate that IFN-γ induces a lytic mechanism in some cancer cells that is opposed by a protein synthesis-dependent resistance mechanism. This suggests that a combination therapy involving IFN-γ and inhibitors of protein synthesis may be useful in the treatment of some cancers.