title: Piroxicam increases colon tumorigenesis and promotes apoptosis in Mlh1 +/- /Apc1638(N/+) mice.
abstract: BACKGROUND
  The present study examines the effect of piroxicam, a non-steroidal anti-inflammatory drug, on tumor development in Mlh1+/- /Apc1638(N/+) mice, in a preclinical model of human colon cancer.
  
  
  METHODS
  Mice were fed AIN-76A diet alone or premixed with piroxicam (60 ppm) for 9 weeks. The number, location and volume of tumors, and apoptosis in the flat mucosa were determined in small and large intestine.
  
  
  RESULTS
  Piroxicam reduced the number of tumors per mouse by 80% in the small intestine (0.1 vs. 0.5, p < 0.05). In contrast, piroxicam increased tumor incidence (82% vs. 10%, p < 0.01), tumor multiplicity (1.2 vs. 0.1, p < 0.01) and tumor volume (2.1 vs. 0.2 mm3, p < 0.01) in the colon. Apoptosis increased in the epithelium of the small intestine.
  
  
  CONCLUSIONS
  Consistent with the increased apoptosis, piroxicam reduced tumors in the small intestine. In the cecum, piroxicam increased tumorigenesis but apoptosis was not decreased, suggesting that other mechanisms besides apoptosis are involved in the differential organ-specific effect on tumorigenesis of piroxicam in this colon cancer model.
authors.affiliation: Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.forename: Kunhua
authors.initials: K
authors.lastname: Fan
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
authors.forename: Mauro
authors.initials: M
authors.lastname: Risio
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
authors.forename: Martin
authors.initials: M
authors.lastname: Lipkin
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D010894:Piroxicam / Q000494:pharmacology*; D011897:Random Allocation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D010894:Piroxicam; D000070957:MutL Protein Homolog 1