Gastroenterology

Gastroenterology

Volume 109, Issue 3, September 1995, Pages 994-998
Gastroenterology

Rapid communications
The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis

https://doi.org/10.1016/0016-5085(95)90411-5Get rights and content

Abstract

Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. Methods: Cell proliferation was studied via immunohistochemistry for proliferating cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. Results: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% ± 4.8% compared with 10% ± 4.3% at baseline; P = 0.01). Conclusions: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

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    Supported by the Clayton Fund, the McAshan Fund, and National Institutes of Health grants CA 53801-03 and 5P030 CA06973. Sulindac was kindly supplied by Merck, Sharpe and Dhome.

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