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

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.

Effect of Glycyrrhiza on the Diuretic Function of Euphorbia kansui: An Ascites Mouse Model

“…Intractable malignant ascites usually have poor prognosis with a life expectancy ranging from 1 to 4 months [ 20 , 21 ]. Although various alternative therapies, including diuretic medicine, have been employed, the evidence regarding their effects on malignant ascites has yet to be fully elucidated [ 22 , 23 ]. GS and GC, the well-known traditional Chinese medicines, have been widely used and proved as effective herbal medicines against malignant ascites in Chinese clinical practice [ 5 , 24 ].…”

Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites

“…After 3 weeks of incubation, ascites cells were collected, washed with phosphate-buffered saline (PBS) three times, and used fresh for assays as described previous (24,25). After washing, the H22 and MethA cells from the ascites were used for further study immediately or maintained in RPMi-1640 medium.…”

“…After euthanasia, the ascites fluid was collected, and the numbers of tumor cells and red blood cells were counted per milliliter per mouse. Before sacrifice, a blood sample was collected through the ophthalmic artery; ascites fluid was completely aspirated as previously described (24). The other five mice of each group were monitored on a daily basis for tumor burden, cachexia and abdominal distension.…”

“…The survival time of each animal was calculated from the day of the beginning of the treatment to euthanasia. The ascites volume of each mouse was calculated as previously described (24). All of the specimens including cells, cell-free ascites fluid, tumors dissected from the peritoneal cavity and the plasma were stored in liquid nitrogen for further analysis.…”

“…To evaluate infectivity, GFP fluorescence intensity was measured by flow cytometry 48 h after incubation; data were analyzed using FLOWJO software. For analysis of apoptosis, flow cytometric analysis (FCM) was performed to detect sub-G1/apoptotic cells in hypotonic buffer as previously described (24).…”