The purpose of this study was to determine the effects of interferon -(IFN -) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN -( AdIFN -) , but not a vector encoding bacterial -galactosidase ( AdLacZ ) , suppressed PC3MM2 tumors in a dose -dependent manner. At the highest dose ( 2Â10 9 plaque -forming units, PFU ) , a single injection of AdIFN -( but not AdLacZ ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN -± treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN -expressed higher levels of IFN -and inducible nitric oxide synthase ( iNOS ) and lower levels of basic fibroblast growth factor ( bFGF ) and transforming growth factor 1 ( TGF -1). In vitro analysis indicated that expression of bFGF and TGF -1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN -gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN -correlated with up -regulation of iNOS and down -regulation of angiogenesis.