Aspirin prevents tumors in a murine model of familial adenomatous polyposis.
BACKGROUND
Both human and murine studies suggest that anti-inflammatory drugs prevent intestinal neoplasia. The purpose of this study was to investigate the role of aspirin as a chemopreventive agent for colorectal cancer.


METHODS
We administered aspirin to the Min/+ mouse, an animal with a germline mutation in Apc, a gene that is essential for normal epithelial cell growth and differentiation. Apc mutation increases cytoplasmic beta-catenin, a regulatory protein associated with the cytoskeleton. Min/+ mice develop multiple intestinal adenomas and exhibit altered cell growth in the preneoplastic intestinal epithelium.


RESULTS
Aspirin decreased the rate of tumor formation in Min/+ mice by 44%. Aspirin also normalized enterocyte growth by increasing apoptosis and proliferation in the preneoplastic intestinal mucosa. Finally, aspirin produced a decrease in intracellular beta-catenin levels, suggesting that modulation of this protein is associated with tumor prevention.


CONCLUSIONS
These data confirm a role for aspirin in suppression of Apc-associated intestinal carcinogenesis.
New York Hospital-Cornell University Medical Center, NY 10021, USA.
N N
NN
Mahmoud
A J
AJ
Dannenberg
J
J
Mestre
R T
RT
Bilinski
M R
MR
Churchill
C
C
Martucci
H
H
Newmark
M M
MM
Bertagnolli
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001710:Biotin; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D004195:Disease Models, Animal; D005260:Female; D018095:Germ-Line Mutation; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013194:Staining and Labeling; D015534:Trans-Activators; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D003856:Deoxyuracil Nucleotides; D015534:Trans-Activators; D051176:beta Catenin; D001710:Biotin; D001241:Aspirin