Inhibition of beta-catenin translocation in rodent colorectal tumors: a novel explanation for the protective effect of nonsteroidal antiinflammatory drugs in colorectal cancer

Dig Dis Sci. 2001 Nov;46(11):2314-21. doi: 10.1023/a:1012326525692.


In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs reduce tumor mass by increasing the rate of tumor cell apoptosis and decreasing proliferation. We have examined beta-catenin as a potential target for these agents in colorectal cancer. Carcinogen-treated rats were treated for 23 weeks with a range of nonsteroidal antiinflammatory drugs. Control animals received vehicle alone. Intracellular beta-catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nuclei). The frequency of nuclear beta-catenin staining correlated directly with the volume of tumor and inversely with the rate of apoptosis. In tumors from treatment groups, the cytoplasmic staining for beta-catenin was unchanged; however, nuclear staining was absent except in the celecoxib group, where it was reduced to a median of 14%. Colorectal tumors from animals treated with NSAIDs show reduced levels of nuclear beta-catenin immunoreactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis
  • Cadherins / drug effects
  • Cadherins / metabolism
  • Carcinogens
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Cytoskeletal Proteins / drug effects*
  • Cytoskeletal Proteins / metabolism
  • Immunohistochemistry
  • Protein Transport / drug effects
  • Rats
  • Trans-Activators*
  • beta Catenin


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cadherins
  • Carcinogens
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • 1,2-Dimethylhydrazine