title: Expression of cyclooxygenase-2 (COX-2) in human esophageal cancer and in vitro inhibition by a specific COX-2 inhibitor, NS-398.
abstract: BACKGROUND
  The purpose of the present paper was to study the expression of cyclooxygenase-2 (COX-2) in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX-2 in esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a COX-2 inhibitor, NS-398, in inducing growth inhibition and apoptosis of human esophageal cancer cells.
  
  
  METHODS
  Biopsy specimens of esophageal dysplasia (n = 21), and surgical resections of SCC (n = 37) were compared with normal esophagus (n = 37) and analyzed by RT-PCR. Human esophageal cells were used for the study. Anti-proliferative effect was measured by MTT, apoptosis was determined by DNA fragmentation assay.
  
  
  RESULTS
  Marked COX-2 expression was shown in SCC and esophageal squamous dysplasia, and no marked COX-2 expression was observed in the normal squamous epithelium, respectively. NS-398 could inhibit esophageal cells growth in a dose-dependent manner, induce apoptosis, and elevate caspase-3 activity in vitro.
  
  
  CONCLUSIONS
  This study provides evidence that COX-2 is upregulated in the majority of cases of squamous dysplasia and SCC of esophagus, and that NS-398 can inhibit growth and induce apoptosis via activating caspase-3 activity in vitro. These results suggest that selective inhibitors of COX-2 may be an effective preventive and therapeutic option for esophageal carcinoma.
authors.affiliation: Institute of Environmental Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Shi
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Lu
authors.forename: Yan-hua
authors.initials: YH
authors.lastname: Su
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Shun-Qing
authors.initials: SQ
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004935:Esophageal Diseases / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D006131:Growth Inhibitors / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage*; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006131:Growth Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases