Albendazole: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation in OVCAR-3 tumor-bearing nude mice.
OBJECTIVE
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.


METHODS
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 x 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.
Pourgholami
Mohammad Hossein
MH
Cancer Research Laboratories, Department of Surgery, St. George Hospital, University of New South Wales, Sydney, New South Wales, Australia.
Yan Cai
Zhao
Z
Lu
Ying
Y
Wang
Lisa
L
Morris
David Lawson
DL
D015766:Albendazole / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001201:Ascites / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D018394:CA-125 Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018394:CA-125 Antigen; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015766:Albendazole