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Departments of Immunopharmacology [P. L. K., K. L. K, D. A. B., W. R. B., C. A. C] and Investigative Toxicology [J. M. L., D. F.], Hoffmann-La Roche Inc., Nutley, New Jersey 07110
The human ovarian carcinoma cell line, NIH:OVCAR-3, possesses high affinity receptors for interleukin-1 (IL-1). Binding experiments with 125I-IL-1
indicate a dissociation constant of approximately 55 pM and the presence of approximately 7800 receptors/cell. These receptors bind both IL-1
and IL-1ß and internalize IL-1. Proliferation of NIH:OVCAR-3 cells is inhibited by IL-1. Half-maximal inhibition is observed with 23 units/ml of IL-1
or IL-1ß. A maximal effect (80% inhibition of cell proliferation) is achieved by treatment of cells with
10 units/ml of IL-1 for 3 days. The antiproliferative effect of IL-1 is blocked by IL-1 receptor antagonist. Light and electron microscopy studies show that IL-1 treatment causes cytopathological changes and a reduction in the number of mitotic figures in NIH:OVCAR-3. IL-1 stimulates prostaglandin E2 release by NIH:OVCAR-3 cells, but this response is unrelated to the antiproliferative effect of IL-1. Interferon-
A (IFN-
A) also inhibits growth of NIH:OVCAR-3 cells in a concentration-dependent manner. Combination of IFN-
A and IL-1 gives synergistic inhibition of NIH:OVCAR-3 cell proliferation. IL-1 alone or in combination with IFN-
A or other agents may be useful for treatment of human ovarian cancer.
1 To whom requests for reprints should be addressed, at Department of Immunopharmacology, Hoffmann-La Roche Inc., Building 86, Nutley, NJ 07110.
2 Present address: Department of Reproductive Endocrinology, The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869.
Received 10/ 8/90. Accepted 1/21/91.
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