Carcinogenesis, Vol. 20, No. 4, 635-640,
April 1999
© 1999 Oxford University Press
Relationship of ß-catenin and Bcl-2 expression to sulindac-induced regression of intestinal tumors in Min mice
Departments of Pathology and Nutrition, University of Tennessee, Knoxville, TN 37901, USA
Non-steroidal anti-inflammatory drugs (NSAIDs) can cause regression of early intestinal tumors and although this is believed to involve cyclooxygenase-2 and apoptosis, the molecular mechanisms remain unclear. Cytoplasmic and nuclear ß-catenin are overexpressed in many of these lesions and Bcl-2, which inhibits apoptosis, may also be elevated during the course of intestinal tumorigenesis. We recently showed that sulindac causes regression of 70–80% of small intestinal tumors in Min/+ mice within 4 days, but does not have the same impact on colonic lesions; after 20 days of treatment the tumor load stabilizes at 10–20% of that in untreated animals. The aim of this study was to determine if NSAID-induced regression of intestinal adenomas might be associated with changes in ß-catenin or Bcl-2 expression. Intestinal tumors from Min/+ mice were harvested after treatment with sulindac for 2, 4 or 20 days and evaluated for expression of ß-catenin and Bcl-2 using immunohistochemistry. There was a 
50% decrease in ß-catenin (P = 0.001) and diminishing Bcl-2 (P = 0.019) in small intestinal tumors harvested between 2 and 4 days of treatment when compared with untreated controls. In contrast, small intestinal tumors from animals treated for 20 days were not significantly different from untreated controls. Colonic tumors expressed higher levels of Bcl-2 than those from the small intestine and did not show any significant changes in either Bcl-2 or ß-catenin expression after treatment. Results suggest that modulation of aberrant ß-catenin expression occurs during NSAID-induced regression of intestinal adenomas and that Bcl-2 may confer resistance to these effects.
Abbreviations: COX-2, cyclooxygenase-2; NSAIDs, non-steroidal anti-inflammatory drugs; PBS, phosphate-buffered saline.
1 To whom correspondence should be addressed Email: mmcentee{at}utk.edu
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