Bile acid induces cyclo-oxygenase-2 expression in cultured human pharyngeal cells: a possible mechanism of carcinogenesis in the upper aerodigestive tract by laryngopharyngeal reflux

Laryngoscope. 2003 Jun;113(6):1059-63. doi: 10.1097/00005537-200306000-00027.


Objectives/hypothesis: Laryngopharyngeal reflux is a common event in patients with head and neck cancer. Bile acid is known to be related to tumor formation in the esophagus through the overexpression of cyclo-oxygenase-2 (COX-2), an enzyme that produces prostanoids. To better understand the mechanism of the laryngopharyngeal reflux-cancer connection, we examined COX-2 expression by bile acid in cultured human pharyngeal mucosa cells.

Methods: COX-2 expression induction by various combinations of chenodeoxycholate and acidity was observed by Western blotting and reverse transcriptase-polymerase chain reaction. COX-2 promoter activity was also measured by luciferase promoter assay.

Results: Chenodeoxycholate, one of the bile acid components, was found to induce COX-2 expression in human pharyngeal cells. Moreover, the induction of COX-2 by chenodeoxycholate was enhanced by acidity in a dose-dependent manner, and the promoter activity of COX-2 was increased by chenodeoxycholate in SNU-1041, a human laryngeal cancer cell line, whereas the transcription of COX-2 was inhibited by actinomycin-D.

Conclusion: Bile salts or acidic conditions, or both, can induce COX-2 expression in normal pharyngeal mucosa, which implies that laryngopharyngeal reflux has a role in the tumorigenesis of the upper aerodigestive tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Acids and Salts / toxicity*
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Chenodeoxycholic Acid / toxicity*
  • Cyclooxygenase 2
  • Dactinomycin / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Enzyme Induction / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / pathology
  • Humans
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Larynx / drug effects
  • Larynx / pathology
  • Membrane Proteins
  • Pharyngeal Neoplasms / genetics*
  • Pharyngeal Neoplasms / pathology
  • Pharynx / drug effects
  • Pharynx / pathology
  • Promoter Regions, Genetic
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology


  • Bile Acids and Salts
  • Isoenzymes
  • Membrane Proteins
  • Chenodeoxycholic Acid
  • Dactinomycin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases