Annals of Oncology Advance Access published online on April 23, 2008
Annals of Oncology, doi:10.1093/annonc/mdn167
Efficient inhibition of cisplatin-resistant human ovarian cancer growth and prolonged survival by gene transferred vesicular stomatitis virus matrix protein in nude mice
1 Department of Gynecology and Obstetrics, West China Second Hospital and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu
2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan
3 Department of Public Health, West China Medical School, Sichuan University, Chengdu 610041, China
* Correspondence to: Prof. X. Zhao, Department of Gynecology and Obstetrics, West China Second Hospital of Sichuan University, No. 20, Section 3, South People's Road, Chengdu, Sichuan, People's Republic of China. Tel: +86-28-85501633; Fax: +86-28-85164060; E-mail: Xia-Zhao{at}126.com
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.
angiogenesis, apoptosis, cisplatin-resistant, ovarian cancer, vesicular stomatitis virus matrix protein (VSVMP)
These authors contributed equally to this work. Received for publication November 2, 2007. Revision received March 19, 2008. Accepted for publication March 20, 2008.