title: Rofecoxib does not inhibit aberrant crypt foci formation but inhibits later steps in the development of experimental colorectal cancer: rofecoxib in experimental colon cancer.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) has been shown to have an important role in carcinogenesis. Elevated COX-2 expression has been reported in several human tumours, including colorectal cancer (CRC) and appears to correlate with survival inversely. Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) can decrease the incidence of CRC, but prolonged administration may cause side effects. Selective COX-2 inhibitors have comparable effects to NSAIDs with reduced side effects. The aim of the present study was to analyse the potential therapeutic role of rofecoxib, a selective COX-2 inhibitor, in experimentally induced rat colorectal tumours.
  
  
  METHODS
  Sixty-three Wistar male rats (33 in the experimental group and 30 in the control group) received subcutaneous injections of 1,2-dimethylhydrazine (DMH). Synchronal with the first injection of DMH in the experimental group, rats were given rofecoxib orally for 6 months, when autopsy was done. Colorectal tumours were evaluated quantitatively and histopathologically for the presence of aberrant crypt foci (ACF), adenomas and adenocarcinomas.
  
  
  RESULTS
  No statistically significant differences were found in the number of dysplastic ACF between the experimental and control groups (p > 0.05). However, a significant lower incidence of adenomas (p < 0.05), adenocarcinomas (p < 0.05) and decreased volume of macroscopically visible tumours (by 42%) was found in the experimental group. Furthermore, no significant differences were evaluated between the groups according to the degree of dysplasia and Dukes stage. In the experimental group, chronic ulcerations were found in the upper gastrointestinal tract in 9% of the rats.
  
  
  CONCLUSIONS
  Our data suggest that rofecoxib effectively inhibits tumour growth and progression but not tumour initiation.
authors.affiliation: Institute of Pathology, Medical Experimental Centre, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. martina.perse@mf.uni-lj.si
authors.forename: Martina
authors.initials: M
authors.lastname: Perse
authors.forename: Ana
authors.initials: A
authors.lastname: Zebic
authors.forename: Anton
authors.initials: A
authors.lastname: Cerar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001707:Biopsy, Needle; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D007783:Lactones; D013450:Sulfones; C116926:rofecoxib