Targeting vascular endothelial growth factor with the monoclonal antibody bevacizumab inhibits human hepatocellular carcinoma cells growing in an orthotopic mouse model.
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Liver resection or transplantation is curative for a subset of patients with localized disease, but treatments for advanced disease are generally toxic and ineffective. Aberrant expression of the vascular endothelial growth factor (VEGF) has been implicated in the progression of HCC and represents a valid target for anticancer therapy. Bevacizumab, a humanized anti-VEGF monoclonal antibody, is currently being evaluated in the treatment of HCC. In addition, other novel anti-angiogenesis agents are being developed in HCC.


OBJECTIVE
This study examines the effect of bevacizumab in a newly characterized orthotopic model of the disease using the human HCC cell line, Hep 3B, and provides preclinical evidence that an anti-angiogenic approach holds promise in HCC.


RESULTS
Administration of bevacizumab 5 mg/kg intraperitoneal twice a week significantly decreased microvessel density in tumours, decreased human serum alpha-fetoprotein measurements and prolonged the time to progression for treatment mice compared with control mice.


CONCLUSIONS
Our findings suggest that targeting VEGF with bevacizumab may be an effective approach to the treatment of HCC and further study of other novel anti-angiogenic agents in HCC is warranted.
Finn
Richard S
RS
Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. rfinn@mednet.ucla.edu
Bentley
Greg
G
Britten
Carolyn D
CD
Amado
Rafael
R
Busuttil
Ronald W
RW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000503:physiopathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D016014:Linear Models; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D000068258:Bevacizumab