Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16683
Revised: April 28, 2014
Accepted: July 24, 2014
Published online: November 28, 2014
Processing time: 322 Days and 12.3 Hours
AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.
METHODS: Azathioprine was administered via drinking water (estimated 6-20 mg/kg body weight per day) to ApcMin/+ and wildtype mice. Control animals received vehicle only (DMSO) dissolved in drinking water. At 15 wk of age all mice were sacrificed and intestines of ApcMin/+ were harvested for evaluation of polyp number. Azathioprine induced toxicity was investigated by immunohistochemical analysis on spleens.
RESULTS: All azathioprine treated mice showed signs of drug-associated toxicity such as weight loss and development of splenic T-cell lymphomas. Although this suggests that the thiopurine concentration was clearly in the therapeutic range, it did not reduce tumor formation (48 ± 3.1 adenomas vs 59 ± 5.7 adenomas, P = 0.148).
CONCLUSION: We conclude that in the absence of inflammation, azathioprine does not affect intestinal tumorigenesis.
Core tip: Treatment with thiopurines is associated with a reduced risk of developing colorectal cancer in patients with inflammatory bowel disease. The molecular target of azathioprine, Rac1 has recently been implicated as a critical player during sporadic intestinal tumorigenesis. Here, we investigated the potential preventive role of azathioprine in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis. Even though all azathioprine treated mice showed signs of drug-associated toxicity, it did not reduce tumor formation. We therefore conclude that in the absence of inflammation azathioprine does not affect intestinal tumorigenesis.