Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats

Surgical stresses, including hepatic ischemia-reperfusion (I/R), promote cancer growth and metastasis. We have reported that continuous hepatic I/R increases liver damage and promoted liver metastasis from colon cancer, whereas intermittent I/R causes less liver damage. We therefore examined whether intermittent I/R could reduce liver metastasis in a rat model.

Adult male Fischer rats was divided between three groups: group A (control), which received laparotomy for 120 min with no liver ischemia; group B (continuous I/R), which received 60 min of 70% partial liver ischemia followed by 60 min of reperfusion; and group C (intermittent I/R), which received 15 min of 70% ischemia and 15 min of reperfusion, repeated four times. Just before closing the abdomen, all animals were inoculated intrasplenically with rat colon adenocarcinoma cells (RCN-H4). Tumor nodules on the liver surface were counted 3 weeks later. In addition, expression of E-selectin mRNA in liver was examined at 1, 3, and 6 h after completing I/R by a reverse transcription-polymerase chain reaction.

Continuous I/R (B) greatly promoted liver metastasis in both ischemic and nonischemic liver lobes, whereas intermittent I/R (C) showed significantly fewer metastasis than group B in both lobes. Significantly less E-selectin mRNA was expressed in group C than in group B.

Intermittent I/R limits expression of E-selectin mRNA and liver metastasis. Intermittent hepatic I/R is less stressful than continuous I/R, minimizing liver metastasis by colon cancer cells through avoidance of E-selectin up-regulation.