RT Journal Article
SR Electronic
T1 Bevacizumab Impairs Hepatocyte Proliferation after Partial Hepatectomy in a Rabbit Model
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5193
OP 5200
VO 32
IS 12
A1 AURELIEN DUPRE
A1 ANDREA PARADISI
A1 STEPHAN LANGONNET
A1 ALESSANDRO GANDINI
A1 PATRICK MEHLEN
A1 MICHEL RIVOIRE
YR 2012
UL http://ar.iiarjournals.org/content/32/12/5193.abstract
AB Background: Bevacizumab is used to treat patients with metastatic colorectal cancer, including those who will undergo liver surgery. The effects of this agent on the regenerative capacity of the liver are unclear. We used a rabbit model of partial hepatectomy to assess the effects of bevacizumab on hepatocyte replication and the expression of genes relevant to angiogenesis and proliferation. Materials and Methods: Thirty rabbits underwent 28% hepatectomy. At the end of the procedure, animals were blindly randomized into two groups. A control group was injected i.v. with saline and the other group with bevacizumab at 50 mg/kg. Three rabbits from each group were sacrificed at days 2, 3, 5, 7 and 14 after hepatectomy. Livers were collected and processed. Hepatocyte proliferation was evaluated by Ki-67 immunostaining and apoptosis by caspase-3 activity. Gene expression of Vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) and Inhibitor α of nuclear factor-κB (IκBα) was determined by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: Compared with controls, hepatocyte proliferation in bevacizumab-treated animals was decreased 1.8-fold at day 3, 1.6-fold at day 5 and 2.1-fold at day 14. Neoangiogenesis began after day 5, with a peak of VEGF mRNA evident at day 7 in both groups. Expression of IκBα, a transcriptional target of Nuclear Factor-κB, increased significantly from baseline only in the control group: at day 2, expression was 179% of the day 0 value in controls versus 112% in the bevacizumab group. Expression of HGF and caspase-3 was similar in the two groups and remained stable over time. Conclusion: A single i.v. injection of bevacizumab impaired hepatocyte proliferation in a rabbit model of partial hepatectomy.