Aspirin prevents tumors in a murine model of familial adenomatous polyposis

Surgery. 1998 Aug;124(2):225-31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / drug therapy*
  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / prevention & control*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Aspirin / pharmacology*
  • Biotin
  • Cadherins / analysis
  • Cadherins / metabolism
  • Cell Division / drug effects
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / metabolism
  • DNA Fragmentation
  • Deoxyuracil Nucleotides
  • Disease Models, Animal
  • Female
  • Germ-Line Mutation
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Staining and Labeling
  • Trans-Activators*
  • beta Catenin

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • Deoxyuracil Nucleotides
  • Trans-Activators
  • beta Catenin
  • Biotin
  • Aspirin