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.
OBJECTIVE
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.


CONCLUSIONS
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.
Sung
Myung-Whun
MW
Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Chongno-Gu, Korea.
Roh
Jong-Lyel
JL
Park
Bum Jung
BJ
Park
Seok Woo
SW
Kwon
Tack-Kyun
TK
Lee
Sang Joon
SJ
Kim
Kwang Hyun
KH
D001647:Bile Acids and Salts / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002635:Chenodeoxycholic Acid / Q000633:toxicity*; D051546:Cyclooxygenase 2; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D007830:Larynx / Q000187:drug effects / Q000473:pathology; D008565:Membrane Proteins; D010610:Pharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D010614:Pharynx / Q000187:drug effects / Q000473:pathology; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D001647:Bile Acids and Salts; D007527:Isoenzymes; D008565:Membrane Proteins; D002635:Chenodeoxycholic Acid; D003609:Dactinomycin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases