Differential Chemopreventive Activity of Sulindac and/or Atorvastatin in Apc+/Min-FCCC Mice With or Without Colorectal Adenomas. Mus musculus

Emerging data suggest that some high-risk subjects benefit more than others from preventive intervention. The goal of this study was to determine the efficacy of sulindac (Sul) and/or atorvastatin (Atorva) against spontaneous colorectal adenomas in Apc+/Min-FCCC mice in which the tumor-bearing status was known at the time of treatment initiation. Administration of Sul/Atorva to tumor-bearing mice led to a 43% reduction in the multiplicity of colorectal adenomas as compared to that of untreated tumor-bearing mice. Atorvastatin completely inhibited the formation of microadenomas in mice that were tumor-free at baseline, with associated decreases in the expression of inflammatory mediators observed. Expression of Hoxb13 and Rprm was enhanced significantly following Sul/Atorva treatment, suggesting the importance of cell cycle regulation in colon tumor inhibition. The tumor status of animals at treatment initiation dictates response to atorvastatin, sulindac and Sul/Atorva. The tumor inhibition observed with Sul/Atorva in tumor-bearing mice was greater than that achieved with either agent alone. Overall design: Male Apc+/Min-FCCC mice were subjected to colonscopy at 6-8 weeks of age. Based on the results of the colonscopic exam, mice were categorized as tumor-free and tumor bearing. Tumor-bearing mice were assigned to receive either meal form of Harlan Teklad 2018SX chow (Harlan Teklad Global Diets, Madison, WI, untreated control) or chow supplemented with sulindac 300 ppm plus atorvastatin 100 ppm. Tumor-free mice were assigned to either the untreated control or the atorvastatin (100 ppm) group. After 7 days of treatment, mice were euthanized and colons were collected and process for gene expression analyses.