Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells

R. F. Souza, K. Shewmake, D. G. Beer, B. Cryer, S. J. Spechler

Research output: Contribution to journalArticle

294 Citations (Scopus)

Abstract

Adenocarcinoma in Barrett's esophagus has been increasing in incidence at a rapid rate for more than two decades. Cyclooxygenase (COX)-2 appears to play an important role in gastrointestinal carcinogenesis, and COX-2 overexpression has been demonstrated both in esophageal adenocarcinomas and in the metaplastic epithelium of Barrett's esophagus. The aim of our study was to determine whether selective inhibition of COX-2 by NS-398 would alter the rates of cell growth and apoptosis in human Barrett's-associated esophageal adenocarcinoma cell lines. COX-1 and COX-2 expression in adenocarcinoma cell lines was determined using reverse transcription-PCR and Western blotting for mRNA and protein, respectively. Esophageal adenocarcinoma cell lines were treated with various concentrations of NS-398 (selective for COX-2 inhibition) and flurbiprofen (selective for COX-1 inhibition). Cell growth was compared in flurbiprofen-treated and untreated tumor cell lines; cell growth and apoptosis were compared in NS-398-treated and untreated tumor cell lines. COX-2 mRNA and protein were detected in two of three cell lines (SEG-1 and FLO); the third cell line, BIC-1, did not express COX-2 mRNA or protein under basal conditions or after stimulation with phorbol 12-myristate 13-acetate. Treatment with COX-1-selective concentrations of flurbiprofen did not affect cell growth in any of the three tumor cell lines. In contrast, treatment with COX-2-selective concentrations of NS-398 significantly suppressed cell growth and increased apoptosis in the cell lines that expressed COX-2 (SEG-1 and FLO), but not in the cell line that did not express COX-2 (BIC-1). We conclude that the administration of a selective inhibitor of COX-2 significantly decreases cell growth and increases apoptosis in Barrett's-associated adenocarcinoma tumor cells that express COX-2. These observations suggest a potential role for selective COX-2 inhibitors in the prevention and treatment of esophageal adenocarcinoma for patients with Barrett's esophagus.

Original languageEnglish (US)
Pages (from-to)5767-5772
Number of pages6
JournalCancer Research
Volume60
Issue number20
StatePublished - Oct 15 2000

Fingerprint

Cyclooxygenase 2
Adenocarcinoma
Apoptosis
Growth
Cell Line
Flurbiprofen
imidazole mustard
Cyclooxygenase 1
Barrett Esophagus
Tumor Cell Line
Cyclooxygenase 2 Inhibitors
Messenger RNA
Proteins
Reverse Transcription
Carcinogenesis
Acetates
Therapeutics
Epithelium
Western Blotting
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. / Souza, R. F.; Shewmake, K.; Beer, D. G.; Cryer, B.; Spechler, S. J.

In: Cancer Research, Vol. 60, No. 20, 15.10.2000, p. 5767-5772.

Research output: Contribution to journalArticle

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abstract = "Adenocarcinoma in Barrett's esophagus has been increasing in incidence at a rapid rate for more than two decades. Cyclooxygenase (COX)-2 appears to play an important role in gastrointestinal carcinogenesis, and COX-2 overexpression has been demonstrated both in esophageal adenocarcinomas and in the metaplastic epithelium of Barrett's esophagus. The aim of our study was to determine whether selective inhibition of COX-2 by NS-398 would alter the rates of cell growth and apoptosis in human Barrett's-associated esophageal adenocarcinoma cell lines. COX-1 and COX-2 expression in adenocarcinoma cell lines was determined using reverse transcription-PCR and Western blotting for mRNA and protein, respectively. Esophageal adenocarcinoma cell lines were treated with various concentrations of NS-398 (selective for COX-2 inhibition) and flurbiprofen (selective for COX-1 inhibition). Cell growth was compared in flurbiprofen-treated and untreated tumor cell lines; cell growth and apoptosis were compared in NS-398-treated and untreated tumor cell lines. COX-2 mRNA and protein were detected in two of three cell lines (SEG-1 and FLO); the third cell line, BIC-1, did not express COX-2 mRNA or protein under basal conditions or after stimulation with phorbol 12-myristate 13-acetate. Treatment with COX-1-selective concentrations of flurbiprofen did not affect cell growth in any of the three tumor cell lines. In contrast, treatment with COX-2-selective concentrations of NS-398 significantly suppressed cell growth and increased apoptosis in the cell lines that expressed COX-2 (SEG-1 and FLO), but not in the cell line that did not express COX-2 (BIC-1). We conclude that the administration of a selective inhibitor of COX-2 significantly decreases cell growth and increases apoptosis in Barrett's-associated adenocarcinoma tumor cells that express COX-2. These observations suggest a potential role for selective COX-2 inhibitors in the prevention and treatment of esophageal adenocarcinoma for patients with Barrett's esophagus.",
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