L S Wang1, K C Chow, Y C Wu. 1. Dept. of Surgery, Veterans General Hospital, Taipei and National Yang-Ming University, Taiwan, ROC. lswang@vghtpe.gov.tw
Abstract
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.
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.
Authors: María A Hidalgo; Alex Romero; Jaime Figueroa; Patricia Cortés; Ilona I Concha; Juan L Hancke; Rafael A Burgos Journal: Br J Pharmacol Date: 2005-03 Impact factor: 8.739
Authors: Miguel Pera; Heidi Nelson; S Vincent Rajkumar; Tonia M Young-Fadok; Lawrence J Burgart Journal: J Gastrointest Surg Date: 2003 Sep-Oct Impact factor: 3.452