Journal
INTERVIROLOGY
Volume 55, Issue 4, Pages 276-286Publisher
KARGER
DOI: 10.1159/000328325
Keywords
Newcastle disease virus; Apoptin; Tumor cells; Apoptosis
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Funding
- earmarked fund for Modern Agro-Industry Technology
- Program for Changjiang Scholars and Innovative Research Team in University
- National Key Laboratory of Veterinary Biotechnology of China [SKLVBF200903]
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Objective: Naturally occurring strains of Newcastle disease virus (NDV) have demonstrated the potential to kill cancer cells in both preclinical and clinical studies. Previous studies showed that apoptin, the VP3 protein of chicken infectious anemia virus, is a p53-independent, Bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in transformed cells. In this study, we tested the hypothesis that apoptin enhances NDV-mediated tumor cell death. Methods: Reverse genetics was used to engineer an oncolytic NDV strain, FMW, to express apoptin. The antitumor effects of the recombinant virus (rFMW/AP) were also evaluated in the tumor cell lines and tumor-bearing mice. Results: Compared to the parental strain FMW, rFMW/AP was more potent in killing A459 and SMMC7721 tumor cells. Recombinant NDV also exhibited higher efficacy in suppressing tumor growth in mice bearing A549-induced tumors. Furthermore, rFMW/AP did not display apparent toxic effects in either normal cells or control mice. Conclusion: Our results suggest that the recombinant NDV expressing apoptin is a promising novel antitumor agent. Copyright (C) 2011 S. Karger AG, Basel
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