, Volume 46, Issue 11, pp 2314-2321

Inhibition of β-Catenin Translocation in Rodent Colorectal Tumors: A Novel Explanation for the Protective Effect of Nonsteroidal Antiinflammatory Drugs in Colorectal Cancer

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Abstract

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 β-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 β-catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nucleii). The frequency of nuclear β-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 β-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 β-catenin immunoreactivity.