PLASMID ENCODING MATRIX PROTEIN OF VESICULAR STOMATITIS VIRUSES AS AN ANTITUMOR AGENT
Aim: Oncolytic effect of vesicular stomatitis virus (VSV) has been proved previously. Aim of the study is to investigate glioma inhibition effect of Matrix (M) protein of VSV in situ. Materials and Methods: A recombinant plasmid encoding VSV M protein (PM) was genetically engineered, and then transfected into cultured C6 gliomas cells in vitro. C6 transfected with Liposome-encapsulated PM (LEPM) was implanted intracranially for tumorigenicity study. In treatment experiment, rats were sequentially established intracranial gliomas with wild-typed C6 cells, and accepted LEPM injection intravenously. Possible mechanism of M protein was studied by using Hoechst staining, PI-stained flow cytometric analysis, TUNEL staining and CD31 staining. Results: M protein can induce generous gliomas lysis in vitro. None of the rats implanted with LEPM-treated cells developed any significant tumors, whereas all rats in control group developed tumors. In treatment experiment, smaller tumor volume and prolonged survival time was found in the LEPM-treated group. Histological studies revealed that possible mechanism were apoptosis and anti-angiogenesis. Conclusion: VSV-M protein can inhibit gliomas growth in vitro and in situ, which indicates such a potential novel biotherapeutic strategy for glioma treatment.
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