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

Cancer Gene Therapy volume 8, pages 497–505 (2001)Cite this article

Abstract

The purpose of this study was to determine the effects of interferon-β (IFN-β) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-β (AdIFN-β), but not a vector encoding bacterial β-galactosidase (AdLacZ), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2×10 9 plaque-forming units, PFU), a single injection of AdIFN-β (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-β–treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-β expressed higher levels of IFN-β and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor β1 (TGF-β1). In vitro analysis indicated that expression of bFGF and TGF-β1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-β gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-β correlated with up-regulation of iNOS and down-regulation of angiogenesis. Cancer Gene Therapy (2001) 8, 497–505

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Acknowledgements

We thank Dr. Isaiah J. Fidler for advice on our research, Dr. Corazon D. Bucana, Donna Reynolds, and Yunfang Wang for technical assistance with immunohistochemical staining, Jacob Lyons for assistance with preparation of adenoviral vectors, and Walter Pagel for critical editorial comments. This study was supported in part by funds from Cancer Center Support Core Grant CA16672 and Grant RPG-98-332 from the American Cancer Society (to Z.D.).

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  1. Guangwen Cao and Jingdong Su: These two authors contributed equally in the project.

Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas

    Guangwen Cao, Jingdong Su, Weixin Lu, Fahao Zhang, Guiling Zhao, Daniele Marteralli & Zhongyun Dong

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Correspondence to Zhongyun Dong.

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Cao, G., Su, J., Lu, W. et al. Adenovirus-mediated interferon-β gene therapy suppresses growth and metastasis of human prostate cancer in nude mice. Cancer Gene Ther 8, 497–505 (2001). https://doi.org/10.1038/sj.cgt.7700333

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