Efficient inhibition of cisplatin-resistant human ovarian cancer growth and prolonged survival by gene transferred vesicular stomatitis virus matrix protein in nude mice

Abstract

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 μg VSVMP/250 μg liposome complex, 50 μg empty plasmid/250 μg 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 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. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.