Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yoshida
Makoto
M
Second Department of Surgery, Fukui Medical University, Fukui, Japan. brandon@fmsrsa.fukui-med.ac.jp
Horiuchi
Tetsuya
T
Uchinami
Masaru
M
Tabo
Takanori
T
Kimura
Narisato
N
Yokomachi
Jun
J
Doi
Koji
K
Nakamura
Tomoaki
T
Tamagawa
Koji
K
Tanaka
Kuniyoshi
K
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D019040:E-Selectin / Q000235:genetics; D007511:Ischemia; D008099:Liver / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015424:Reperfusion; D013312:Stress, Physiological; D013514:Surgical Procedures, Operative / Q000009:adverse effects; D014407:Tumor Cells, Cultured
D019040:E-Selectin; D012333:RNA, Messenger