Expression of a resistance mechanism in ovarian and cervical carcinoma cells prevents their lysis by gamma-interferon.
Despite extensive evidence that recombinant human gamma-interferon (IFN-gamma) exerts antiproliferative effects on a variety of cancer cell lines, IFN-gamma has not been shown to lyse cells in vitro. In order to determine whether some cancer cells might actively resist lysis by IFN-gamma, 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-gamma. In a 24-h assay involving release of 51Cr from cells, none of these cell lines was lysed by IFN-gamma, 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-gamma 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-gamma 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-gamma and inhibitors of protein synthesis may be useful in the treatment of some cancers.
Massad
L S
LS
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110.
Mutch
D G
DG
Powell
C B
CB
Kao
M S
MS
Collins
J L
JL
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D004351:Drug Resistance; D004640:Emetine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D010051:Ovarian Neoplasms; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects; D002583:Uterine Cervical Neoplasms
D011994:Recombinant Proteins; D003609:Dactinomycin; D007371:Interferon-gamma; D004640:Emetine