title: Growth inhibitory effect of celecoxib and rofecoxib on human colorectal carcinoma cell lines.
abstract: BACKGROUND
  Epidemiological studies have revealed a protective effect of NSAIDs, which principally target cyclooxygenase (COX)-1 and COX-2, on the development of colorectal cancer. Increased expression of COX-2 was shown in colorectal adenocarcinoma. However, some effects were shown to be COX-independent. Here, we compared two selective COX-2 inhibitors for their effect on the growth of colorectal tumour cells in vitro.
  
  
  METHODS
  Fifteen tumour cell lines were characterized for COX-1 and COX-2 expression by Western blot and RT-PCR. The effect of celecoxib and rofecoxib on their growth was assessed by staining of DNA with crystal violet.
  
  
  RESULTS
  COX-2 expression varied among cell lines, whereas COX-1 was always expressed. Rofecoxib displayed a limited dose-related effect on cell proliferation, whereas celecoxib strongly inhibited cell growth at high concentrations. Both effects appeared COX-2-independent.
  
  
  CONCLUSIONS
  Rofecoxib, which is devoid of apoptotic effect at high concentration but efficient at pharmacological concentrations, revealed a potential new mechanism of action of NSAIDs towards colorectal cancer.
authors.affiliation: Centre de Recherche en Nutrition Humaine de Nantes, INSERM U539, CHU Hôtel-Dieu, 44035 Nantes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouancheau
authors.forename: Alexis
authors.initials: A
authors.lastname: Broquet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bezieau
authors.forename: Marc G
authors.initials: MG
authors.lastname: Denis
authors.forename: Christian
authors.initials: C
authors.lastname: Bonnet
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Heymann
authors.forename: Anne
authors.initials: A
authors.lastname: Jarry
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Galmiche
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
mesh_terms: D018938:Caco-2 Cells; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008565:Membrane Proteins; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib