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

被引:29
作者
Brown, WA [1 ]
Skinner, SA [1 ]
Vogiagis, D [1 ]
O'Brien, PE [1 ]
机构
[1] Monash Univ, Alfred Hosp, Dept Surg, Prahran, Vic 3181, Australia
关键词
beta-catenin; nonsteroidal antiinflammatory drugs; colorectal cancer; immunohistochemistry; apoptosis;
D O I
10.1023/A:1012326525692
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 nucleii). 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.
引用
收藏
页码:2314 / 2321
页数:8
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