Effect of ACE inhibitors and angiotensin II receptor antagonists in a mouse model of colorectal cancer liver metastases.
OBJECTIVE
Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II type I receptor (AT1R) antagonists are commonly used as a treatment for hypertension. Recent experimental and population studies have suggested that these agents may exert an inhibitory effect on malignancy, possibly through anti-angiogenic pathways. The aim of this study was to investigate the effect of an ACE-I (captopril) and an AT1R antagonist (irbesartan) in colorectal cancer liver metastases.


METHODS
The effect of captopril and irbesartan on tumor growth was investigated in a mouse model using quantitative stereological and histological analysis. Tumor microcirculation was assessed by microvascular resin casting. A survival study was also carried out.


RESULTS
Both captopril and irbesartan markedly decreased tumor growth when compared to control (P = 0.003 and P = 0.004, respectively). However, there was no significant difference in survival or tumor necrosis for either of the drugs. Tumor microvasculature exhibited a reduction in central microvascular density, with constriction and tapering of vessels.


CONCLUSIONS
Captopril and irbesartan caused a marked reduction in volume of colorectal cancer liver metastases and caused changes in tumor microvasculature. However, there was no difference in percentage tumor necrosis or improvements in survival. Further investigation is needed to identify the mode of action of these agents.
Neo
Jaclyn H
JH
Department of Surgery, The University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia. j.neo@pgrad.unimelb.edu.au
Malcontenti-Wilson
Cathy
C
Muralidharan
Vijayaragavan
V
Christophi
Christopher
C
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D000077405:Irbesartan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008855:Microscopy, Electron, Scanning; D009336:Necrosis; D013777:Tetrazoles / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; D000077405:Irbesartan