Inhibition of beta-catenin translocation in rodent colorectal tumors - A novel explanation for the protective effect of nonsteroidal antiinflammatorydrugs in colorectal cancer

In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs re duce tumor mass by increasing the rate of tumor cell apoptosis and decreasi ng 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 anim als received vehicle alone. Intracellular beta -catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen i n the cytoplasm and nucleus (median 24% of nucleii). The frequency of nucle ar 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 stai ning was absent except in the celecoxib group, where it was reduced to a me dian of 14%. Colorectal tumors from animals treated with NSAIDs show reduce d levels of nuclear beta -catenin immunoreactivity.