Expression of cyclooxygenase-2 (COX-2) in human esophageal cancer and in vitro inhibition by a specific COX-2 inhibitor, NS-398

J Gastroenterol Hepatol. 2004 Jun;19(6):638-42. doi: 10.1111/j.1440-1746.2004.03345.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / physiopathology
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / drug effects
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Esophageal Diseases / enzymology
  • Esophageal Diseases / pathology
  • Esophageal Diseases / physiopathology
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / physiopathology
  • Growth Inhibitors / administration & dosage*
  • Humans
  • In Vitro Techniques
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Nitrobenzenes / administration & dosage*
  • Polymerase Chain Reaction
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Sulfonamides / administration & dosage*
  • Up-Regulation

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Growth Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • CASP3 protein, human
  • Caspase 3
  • Caspases