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. Aim: 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 α-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.