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.
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