Effects of platelet activating factor, butyrate and interleukin-6 on cyclooxygenase-2 expression in human esophageal cancer cells.
BACKGROUND
Epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of esophageal squamous cell carcinoma (ESCC) by taking cyclooxygenase (COX) as the target enzyme. The pathophysiological regulation of COX-2 may play a role in carcinogenesis and in disease progression of esophageal carcinoma.


METHODS
59 ESCC samples were used to assess COX-2 expression in the tumor cells and four ESCC cell lines to investigate the effects of phorbol myristate acetate (PMA), platelet activating factor (PAF), n-sodium butyrate (n-BT) and interleukin-6 (IL-6) on the expression of COX-2. Expression of COX-2 was determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Production of PGE2 was measured by a competitive enzyme immunoassay (CEIA).


RESULTS
COX-2 expression was detected in 54.2% (32/59) of the pathological sections by IHC. COX-2 expression in ESCC cells was significantly increased following treatment with PAF and n-BT. Increased production of PGE2 was detected in the culture media, and the secreted PGE2 in the culture media was proportional to the increased COX-2 expression. The addition of IL-6 could also enhance COX-2 expression in ESCC cells. While NSAIDs could inhibit enzymatic activity of COX-2, they did not inhibit COX-2 gene expression in ESCC cells. PKC inhibitor, however, could abrogate PMA-induced COX-2 gene expression, but it did not block IL-6-induced COX-2 expression.


CONCLUSIONS
Our data suggest that COX-2 expression in ESCC cells could be upregulated by PMA, PAF, n-BT and IL-6. Nonetheless, IL-6-induced COX-2 expression could be independent of PKC activation.
Wang
L S
LS
Dept. of Surgery, Veterans General Hospital, Taipei and National Yang-Ming University, Taiwan, ROC. lswang@vghtpe.gov.tw
Chow
K C
KC
Wu
Y C
YC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002087:Butyrates; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate