Adenovirus-mediated interferon-ss gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

The purpose of this study was to determine the effects of interferon-beta ( IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding muri ne IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta -galacto sidase (AdLac Z), suppressed PC3MM2 tumors in a dose-dependent manner. At t he highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLac Z) suppressed orthotopic PC3MM2 tumors and develo pment of metastasis by 80%, and eradicated the tumors in 20% of mice. Immun ohistochemical staining showed that AdIFN-beta -treated tumors contained fe wer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN- beta expressed higher levels of IFN-beta and inducible nitric oxide synthas e (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and tran sforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumo ral delivery of the IFN-beta gene with adenoviral vectors could be an effec tive therapy for prostate cancer and that tumor suppression by AdIFN-beta c orrelated with up-regulation of iNOS and down-regulation of angiogenesis.