title: Chemopreventive effect of mofezolac on beef tallow diet/azoxymethane-induced colon carcinogenesis in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  This study suggested that mofezolac suppressed beef tallow-promoted colon carcinogenesis in rats, which probably was, appropriate for populations with high fat intake.
authors.affiliation: Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Lujie
authors.initials: L
authors.lastname: Miao
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Shiraishi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fujise
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kuroki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kakimoto
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sakata
authors.forename: Tooru
authors.initials: T
authors.lastname: Takashima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
authors.forename: Xueliang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D015153:Blotting, Western; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D004041:Dietary Fats / Q000633:toxicity*; D005223:Fats; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D005223:Fats; D007555:Isoxazoles; C013698:tallow; D001397:Azoxymethane; C054999:mofezolac