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Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation

Cancer Gene Therapy volume 20, pages 178–185 (2013)Cite this article

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Abstract

Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6–8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 μg VSVMP/250 μg liposome complexes, 50 μg empty plasmid/250 μg liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation.

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Abbreviations

e–p:

50 μg empty plasmid pcDNA3.1/250 μg liposome complexes

i.p.:

intraperitoneally

NS:

0.9% NaCl solution

VSV:

vesicular stomatitis virus

VSVMP:

VSV matrix protein-cDNA/250 μg liposome complexes

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Acknowledgements

This study was supported, in part, by the Project of the National Natural Science Foundation of China (no. 81071862).

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Authors and Affiliations

  1. The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Y Zhou, F Wen, P Zhang, R Tang & Q Li

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Correspondence to Q Li.

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Zhou, Y., Wen, F., Zhang, P. et al. Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation. Cancer Gene Ther 20, 178–185 (2013). https://doi.org/10.1038/cgt.2013.7

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