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

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110

Despite extensive evidence that recombinant human -interferon (IFN-) exerts antiproliferative effects on a variety of cancer cell lines, IFN- has not been shown to lyse cells in vitro. In order to determine whether some cancer cells might actively resist lysis by IFN-, 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-. In a 24-h assay involving release of ⁵¹Cr from cells, none of these cell lines was lysed by IFN-, 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- 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- 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- and inhibitors of protein synthesis may be useful in the treatment of some cancers.

¹ To whom reprint requests should be addressed, at Department of Obstetrics/Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, MO 63110.

Received 2/20/90. Revised 4/24/90.