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J Surg Res. 2008 Aug;148(2):158-63. doi: 10.1016/j.jss.2007.12.787. Epub 2008 Jan 29.

Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats.

Author information

1
Second Department of Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. hanil@ommc-hp.jp

Abstract

BACKGROUND:

In liver surgery, the hepatic pedicle often is clamped to reduce blood loss, and later unclamped, representing hepatic ischemia and reperfusion (I/R) with induction of hypoxia. Vascular endothelial growth factor (VEGF) expression reportedly is induced by hypoxia; further, some cancer cells express the VEGF receptor (flt-1, flk-1/KDR). We hypothesized that I/R-induced VEGF expression could enhance growth of microscopic tumor via VEGF receptors on tumor cells, thus promoting liver metastasis in a rat model.

MATERIALS AND METHODS:

Time-dependent VEGF expression in liver and plasma was determined by enzyme-linked immunosorbent assay in rats subjected to 60 min of 70% hepatic I/R (I/R group). Other rats given an intrasplenic inoculation of a rat colon adenocarcinoma cell line (RCH-H4) were divided 3 days later into three groups: group A, untreated; group B, sham operation; group C, 70% I/R for 60 min. Liver metastasis was evaluated on day 14. Expression of flt-1 and flk-1/KDR was examined in RCN-H4 cells, and effects of exogenous VEGF on RCN-H4 cell proliferation were determined by MTT assays.

RESULTS:

Hepatic VEGF expression increased significantly in the I/R group compared to the control group. Liver metastasis was more extensive in group C than in groups A and B. RCN-H4 cells expressed flt-1 and flk-1/KDR, while exogenous VEGF increased RCN-H4 cell proliferation.

CONCLUSION:

Hepatic ischemia reperfusion leads to induction of VEGF and this is associated with increased tumor burden in an animal model of colon cancer metastasis.

PMID:
18468635
DOI:
10.1016/j.jss.2007.12.787
[Indexed for MEDLINE]
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