Albendazole: a Potent Inhibitor of Vascular Endothelial Growth Factor and Malignant Ascites Formation in OVCAR-3 Tumor-Bearing Nude Mice
- 15 March 2006
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 12 (6), 1928-1935
- https://doi.org/10.1158/1078-0432.ccr-05-1181
Abstract
Purpose: Angiogenesis and vessel hyperpermeability are the two factors leading to the formation of ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in malignant ascites formation. We have recently shown that albendazole inhibits peritoneal growth of human colorectal cancer cells (HT-29). The present study was designed to find out if albendazole can suppress ascites formation in ascites-producing peritoneal carcinomatosis. Experimental design: Female nude mice bearing peritoneal tumors of human ovarian cancer cells (OVCAR-3) were treated with albendazole. Following i.p. inoculation and ascites development, mice were given i.p. albendazole (150 mg/kg) or the vehicle × 3 weekly for 4 weeks. Results: Whereas vehicle-treated mice developed overt ascites requiring repeated aspiration, ascites formation in the albendazole-treated mice was markedly suppressed. As a result of this, 7 of 10 mice from the control group had to be euthanized before the course of treatment was over. Suppressed ascites production and reduced tumor vascularity observed was a result of dramatic reduction in tumor VEGF production as revealed by profoundly lower VEGF ascites fluid and plasma levels. In vitro, incubation of SKOV-3 cells with various concentrations of albendazole led to significant dose-dependent inhibition of VEGF secretion. Examination of floating tumor cells collected from the peritoneal wash revealed profound down-regulation of VEGF mRNA in albendazole-treated mice. Conclusions: These findings suggest for the first time that in nude mice bearing OVCAR-3 peritoneal tumors, by inhibiting VEGF production, albendazole abolishes tumor angiogenesis and ascites formation.Keywords
This publication has 34 references indexed in Scilit:
- Proinvasive Properties of Ovarian Cancer Ascites-Derived Membrane VesiclesCancer Research, 2004
- Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancerNature Reviews Drug Discovery, 2004
- A Genetically Defined Model for Human Ovarian CancerCancer Research, 2004
- Bikunin plus paclitaxel markedly reduces tumor burden and ascites in mouse model of ovarian cancerInternational Journal of Cancer, 2004
- The biology of VEGF and its receptorsNature Medicine, 2003
- AnthelminticsDrugs, 1997
- Inhibition of Growth and Metastasis of Ovarian Carcinoma by Administering a Drug Capable of Interfering with Vascular Endothelial Growth Factor ActivityJapanese Journal of Cancer Research, 1996
- Expression of Vascular Endothelial Growt Factor and Its Receptors fit and KDR in Ovarian CarcinomaJNCI Journal of the National Cancer Institute, 1995
- Mode of action of benzimidazolesParasitology Today, 1990
- Albendazole in hydatid disease.BMJ, 1983