Increased cyclooxygenase-2 expression in human squamous cell carcinomas of the head and neck and inhibition of proliferation by nonsteroidal anti-inflammatory drugs

Anticancer Res. 2002 Jul-Aug;22(4):2089-96.

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cyclooxygenase 2
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Indomethacin / pharmacology
  • Isoenzymes / analysis
  • Isoenzymes / genetics*
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Sulfonamides / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers, Tumor
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Indomethacin