BACKGROUND: The vesicular stomatitis virus matrix protein (VSVMP) has been receiving attention as an anticancer agent because of its ability of inducing apoptosis. MATERIALS AND METHODS: Nude mice bearing A2780s and A2780cp ovarian tumors were treated twice weekly with i.v. administration of 50 microg VSVMP/250 mug liposome complex, 50 microg empty plasmid/250 microg liposome complex, 0.9% NaCl solution or weekly with i.p. administration of cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. TUNEL assay and CD34 vessel staining were conducted in tumor tissue. Antiangiogenesis in vivo were determined by sponge assay. Antiproliferative and apoptosis-inducing activities of VSVMP in vitro were tested on MS1 murine endothelial cells and four human ovarian cancer cell lines: A2780s, A2780cp, HO8910 and COC1. RESULTS: Administration of VSVMP resulted in significant inhibition (87%-98% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts, and prolonged the survival of the treated mice. Complete tumor regression happened in VSVMP-treated mice in both tumor models. These antitumor responses were associated with marked increases in tumor apoptosis and reductions in intratumoral microvessel density. CONCLUSIONS: Our data indicate that VSVMP may provide an effective approach to inhibit both cisplatin-sensitive and -resistant human ovarian cancer growth with minimal side-effects.
BACKGROUND: The vesicular stomatitis virus matrix protein (VSVMP) has been receiving attention as an anticancer agent because of its ability of inducing apoptosis. MATERIALS AND METHODS:Nude mice bearing A2780s and A2780cp ovarian tumors were treated twice weekly with i.v. administration of 50 microg VSVMP/250 mug liposome complex, 50 microg empty plasmid/250 microg liposome complex, 0.9% NaCl solution or weekly with i.p. administration of cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. TUNEL assay and CD34 vessel staining were conducted in tumor tissue. Antiangiogenesis in vivo were determined by sponge assay. Antiproliferative and apoptosis-inducing activities of VSVMP in vitro were tested on MS1murine endothelial cells and four humanovarian cancer cell lines: A2780s, A2780cp, HO8910 and COC1. RESULTS: Administration of VSVMP resulted in significant inhibition (87%-98% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts, and prolonged the survival of the treated mice. Complete tumor regression happened in VSVMP-treated mice in both tumor models. These antitumor responses were associated with marked increases in tumor apoptosis and reductions in intratumoral microvessel density. CONCLUSIONS: Our data indicate that VSVMP may provide an effective approach to inhibit both cisplatin-sensitive and -resistant humanovarian cancer growth with minimal side-effects.