| Objective: Vesicular stomatitis virus (VSV), a newly developed oncolyticvirus, can preferentially replicate in malignant cells and eventually induceapoptosis. Recent studies have demonstrated that it is the matrix protein (MP),a structural component of the virion, that causes considerablecytopathogenesis of VSV in the absence of other viral components. Manyresearches regarding VSVMP focused on its ability to induce apoptosis invitro. In the present study, the antitumor effect of a recombinant plasmidencoding VSVMP on human ovarian cancer and its apoptosis-inducingefficacy in vitro and in vivo were further investigated.Methods: SKOV3 ovarian cancer cells were transfected with VSVMP-p andexamined for apoptosis by Hoechst 33258 staining and flow cytometricanalysis. For in vivo study, intraperitoneal ovarian carcinomatosis models innude mice were established and randomly assigned into four groups toreceive six twice-weekly i.p. administrations of VSVMP-p/liposomecomplexes, empty plasmid/liposome complexes, liposome alone or 0.9％ NaCl solution, respectively. The weight of intraperitoneal carcinomatosis andthe survival were monitored. Tumor tissues were inspected for apoptosis byTUNEL and Hoechst-33258 assay.Results: Plentiful apoptosis were observed in SKOV3 cells transfected withVSVMP-p. VSVMP-p reduced intraperitoneal tumor weight by about～90％compared with control agents (p＜0.05) and significantly prolonged thesurvival of tumor-bearing mice (p＜0.05), with in vivo apoptosis index of12.6±2.7％which was much higher than that of control groups (＜4％)(p＜0.05). Interestingly, this antitumor effect was accompanied by anoticeable NK cell accumulation. The treatment with VSVMP-p was devoidof any conspicuous toxicity.Conclusions: These observations suggest that VSVMP-p have strongantitumor effects by inducing apoptosis and possibly NK cell-mediated tumorresistance mechanisms, and it may be a potentially effective novel therapyagainst human ovarian cancer. |
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