Antiproliferative effect of interleukin-1 on human ovarian carcinoma cell line (NIH:OVCAR-3).
The human ovarian carcinoma cell line, NIH:OVCAR-3, possesses high affinity receptors for interleukin-1 (IL-1). Binding experiments with 125I-IL-1 alpha indicate a dissociation constant of approximately 55 pM and the presence of approximately 7800 receptors/cell. These receptors bind both IL-1 alpha and IL-1 beta and internalize IL-1. Proliferation is NIH:OVCAR-3 cells is inhibited by IL-1. Half-maximal inhibition is observed with 2-3 units/ml of IL-1 alpha or IL-1 beta. A maximal effect (80% inhibition of cell proliferation) is achieved by treatment of cells with greater than or equal to 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-alpha A (IFN-alpha A) also inhibits growth of NIH:OVCAR-3 cells in a concentration-dependent manner. Combination of IFN-alpha A and IL-1 gives synergistic inhibition of NIH:OVCAR-3 cell proliferation. IL-1 alone or in combination with IFN-alpha A or other agents may be useful for treatment of human ovarian cancer.
Kilian
P L
PL
Department of Immunopharmacology, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Kaffka
K L
KL
Biondi
D A
DA
Lipman
J M
JM
Benjamin
W R
WR
Feldman
D
D
Campen
C A
CA
D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D017471:Receptors, Interferon; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017471:Receptors, Interferon