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Participation of growth factors and intracellular cAMP in direct antiproliferative action of interferon alpha (IFN-alpha) was investigated in PC-3 human prostate carcinoma cell line. IFN-alpha inhibited proliferation of PC-3 cells in a dose-dependent manner in vitro, and the effect was reversible. Fibroblast growth factor, epidermal growth factor and platelet-derived growth factor, when added to the culture medium, showed no effect on growth of PC-3 cells in presence or absence of IFN-alpha. Transforming growth factor beta (TGF-beta) significantly inhibited PC-3 cell growth, and the effect was additived to that of IFN-alpha. TGF-beta content in conditioned medium of PC-3 cells was not affected by treatment with IFN-alpha. On the other hand, IFN-alpha increased intracellular cAMP concentration about 20-fold. Dibutyryl cAMP and reagents which elevated intracellular cAMP level also inhibited PC-3 cell growth. These indicated that direct antiproliferative effect of IFN-alpha on PC-3 cells was at least partly mediated by cAMP, and that neither growth factors nor a growth inhibitor participated in the action of IFN-alpha.

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