Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
Int J Mol Med. 2013 Jul;32(1):93-100. doi: 10.3892/ijmm.2013.1376. Epub 2013 May 10.
Cyclooxygenase-2 (COX-2) participates in cancer invasion and metastasis by decreasing the expression of E-cadherin. However, the molecular mechanisms through which COX-2 regulates E-cadherin expression and function have not yet been fully elucidated. The aim of this study was to investigate the possible molecular mechanisms through which COX-2 regulates E-cadherin expression in gastric cancer. The mRNA and protein expression of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin was detected in gastric cancer cells by quantitative PCR and western blot analysis, respectively. The expression of these genes was also detected in healthy gastric mucosa and gastric cancer tissues by immunohistochemistry. We detected various levels of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin expression in the normal gastric mucosa and cancer tissues; however, the expression patterns differed: the increased expression of COX-2, NF-κB and Snail was observed in the gastric cancer tissues, whereas there was a considerable reduction in E-cadherin expression in the cancer tissues compared to the normal gastric mucosa. The expression patterns of COX-2, NF-κB and Snail were similar. The increased expression of COX-2 in the gastric cancer tissues closely correlated with the increased expression of NF-κB and Snail, but inversely correlated with the expression of E-cadherin. Treatment of the SGC7901 cells (which express high levels of COX-2) with celecoxib, a COX-2 inhibitor, not only led to a marked dose- and time-dependent decrease in the expression of COX-2, NF-κB and Snail, but also led to a significant increase in the expression of E-cadherin, and this was associated with a reduction in cell invasion. By contrast, the same treatment did not alter the expression of these genes in another gastric cancer cell line, MGC803 (which barely expresses COX-2). These data suggest that COX-2 regulates the expression of E-cadherin through the NF-κB and Snail signaling pathway in gastric cancer.
环氧化酶-2（COX-2）通过降低 E-钙黏蛋白的表达参与癌症的侵袭和转移。然而，COX-2 调节 E-钙黏蛋白表达和功能的分子机制尚未完全阐明。本研究旨在探讨 COX-2 调节胃癌中 E-钙黏蛋白表达的可能分子机制。通过定量 PCR 和 Western blot 分析分别检测胃癌细胞中 COX-2、核因子-κB（NF-κB）、Snail 和 E-钙黏蛋白的 mRNA 和蛋白表达。免疫组织化学检测正常胃黏膜和胃癌组织中这些基因的表达。我们检测了正常胃黏膜和癌组织中各种水平的 COX-2、核因子-κB（NF-κB）、Snail 和 E-钙黏蛋白表达；然而，表达模式不同：胃癌组织中 COX-2、NF-κB 和 Snail 的表达增加，而 E-钙黏蛋白的表达与正常胃黏膜相比显著降低。COX-2、NF-κB 和 Snail 的表达模式相似。胃癌组织中 COX-2 的表达增加与 NF-κB 和 Snail 的表达增加密切相关，但与 E-钙黏蛋白的表达呈负相关。用 COX-2 抑制剂塞来昔布处理表达高水平 COX-2 的 SGC7901 细胞不仅导致 COX-2、NF-κB 和 Snail 的表达呈剂量和时间依赖性显著降低，而且导致 E-钙黏蛋白的表达显著增加，这与细胞侵袭减少有关。相比之下，相同的处理并没有改变另一种胃癌细胞系 MGC803（几乎不表达 COX-2）中这些基因的表达。这些数据表明 COX-2 通过 NF-κB 和 Snail 信号通路调节胃癌中 E-钙黏蛋白的表达。
