Chemopreventive effect of mofezolac on beef tallow diet/azoxymethane-induced colon carcinogenesis in rats
Miao, L.; Shiraishi, R.; Fujise, T.; Kuroki, T.; Kakimoto, T.; Sakata, Y.; Takashima, T.; Iwakiri, R.; Fujimoto, K.; Shi, R.; Li, X.
Hepato-Gastroenterology 58(105): 81-88
2011
ISSN/ISBN: 0172-6390 PMID: 21510291 Document Number: 652121
We have previously shown that long-term consumption of 10% beef tallow diet promotes colon carcinogenesis in both saline- and azoxymethane (AOM)-treated rats. Here, we investigated the effects of mofezolac, a selective COX-1 inhibitor, on beef tallow-fed rats with saline- or AOM treatment. Male SD rats were intraperitoneally injected with saline or AOM and fed 10% beef tallow diet with or without 1200 ppm mofezolac. At 12 weeks, aberrant crypt foci (ACF) were examined. At 44 weeks, tumors were counted, the proliferation and expression of COX-1 and 8-catenin on normal-appearing colonic mucosa was evaluated using the BrdU incorporation assay and Western blotting respectively. Mofezolac decreased the number of ACF at 12 weeks (p < 0.05) and reduced tumor multiplicity and incidence at 44 weeks in beef tallow-fed rats with AOM treatment (p < 0.05). At 44 weeks, reduction of the BrdU-positive cells (p < 0.05) and beneficial distribution changes of these cells within the colon crypts in both groups with mofezolac supplementation were observed. The expression of COX-1 and beta-catenin also reduced in mofezolac-added groups simultaneously (p < 0.05). This study suggested that mofezolac suppressed beef tallow-promoted colon carcinogenesis in rats, which probably was, appropriate for populations with high fat intake.