Evaluation of vesicular stomatitis virus mutant as an oncolytic agent against prostate cancer.

Abstract

BACKGROUND To date, limited options are available to treat malignant prostate cancer, and novel strategies need to be developed. Oncolytic viruses (OV) that have preferential replication capabilities in cancer cells rather than normal cells represent one promising alternative for treating malignant tumors. Vesicular stomatitis virus (VSV) is a non-segmented, negative-strand RNA virus with the inherent capability to selectively kill tumor cells. The aim of this study was to evaluate the potential of VSV-ΔM51-GFP as an effective therapeutic agent for treating prostate tumors. METHODS For in vitro experiments, DU145 and PC3 cell lines were treated with VSV-ΔM51-GFP. Viral titers were quantified using plaque assays. Cytotoxicity was performed by MTT analysis. IFN-β production was measured using a Human IFN-β detection ELISA Kit. The detection of apoptosis was performed via Annexin-V-FITC staining method and analyzed with flow cytometry. The in vivo antitumor efficacy of VSV-ΔM51-GFP in a xenograft mice prostate tumor model. RESULTS It was observed that VSV-ΔM51-GFP can efficiently replicate and lyse human prostate cancer cells and that this virus has reduced toxicity against normal human prostate epithelial cells in vitro. VSV-ΔM51-GFP in the induction of apoptosis in DU145 cells and PC3 cells. Furthermore, in a xenograft tumor animal model, nude mice bearing replication-competent VSV-ΔM51-GFP were able to eradicate malignant cells while leaving normal tissue relatively unaffected. The survival of the tumor-burdened animals treated with VSV-ΔM51-GFP may also be significantly prolonged compared to mock-infected animals. CONCLUSIONS VSV-ΔM51-GFP showed promising oncolytic activity for treating prostate cancer.

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