title: Increased cyclooxygenase-2 expression in human squamous cell carcinomas of the head and neck and inhibition of proliferation by nonsteroidal anti-inflammatory drugs.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) has been found to be up-regulated in several types of human cancers and its role in the carcinogenic process has been proposed The aim of this study was to examine the expression of COX-2 in human squamous cell carcinoma of the head and neck (SCCHN) and to find out the effects of COX-2 inhibitors on the growth of cultured cells.
  
  
  METHODS
  We investigated the effect of indomethacin and NS-398 at various concentrations on the growth of SCCHN cell lines using cell proliferation assay, cell cycle analysis and quantification of apoptosis.
  
  
  RESULTS
  Immunostaining revealed a significantly increased COX-2 expression in tumor tissues compared with normal controls (p<0.05). Western blotting analysis using a COX-2 antibody, indicated that seven SCCHN cell lines tested constitutively expressed COX-2 protein. Treatment of head and neck cancer cells with NS-398 (10-200 microM) or indomethacin (50-1000 microM) for 72 hours showed a significant dose-dependent inhibition of cell growth (p<0.01) and a significant increase in the number of cells in the G0/G1-phases of the cell cycle with a concomitant reduction at the S-phase in a dose-dependent manner (p<0.05). NS-398 was more effective in cell cycle arrest and growth inhibition than indomethacin (p<0.05) and induced significant apoptosis in two out of three SCCHN cell lines tested at the concentration of 100 microM.
  
  
  CONCLUSIONS
  Our study showed that COX-2 could be a participant in carcinogenesis of SCCHN and that COX-2 inhibitors would be a potential tool for the treatment and prevention of SCCHN.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Korea.
authors.forename: Dong W
authors.initials: DW
authors.lastname: Lee
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Weon-Jin
authors.initials: WJ
authors.lastname: Seong
authors.forename: Jong-Lyel
authors.initials: JL
authors.lastname: Roh
authors.forename: Bumjung
authors.initials: B
authors.lastname: Park
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin