Interaction between cyclooxygenase-2, Snail, and E-cadherin in gastric cancer cells
Interaction between cyclooxygenase-2, Snail, and E-cadherin in gastric cancer cells
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胃癌细胞中 cyclooxygenase-2、Snail 和 E-cadherin 之间的相互作用
DOI：
10.3748/wjg.v19.i37.6265
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发表时间：
2013-10-07
影响因子：
4.3
通讯作者：
Qiao, Liang
中科院分区：
文献类型：
--
作者：
Liu, Xiao-Jun;Chen, Zhao-Feng;Qiao, Liang
目的：为探讨环氧合酶-2（cyclooxygenase-2，考克斯-2）对胃癌细胞E-cadherin表达的调控机制，从mRNA和蛋白水平检测考克斯-2在人胃癌细胞系SGC-7901、BGC-823、MGC-803和AGS中的表达。选择富含考克斯-2的细胞系SGC-7901用于后续实验。采用siRNA介导的基因敲低研究考克斯-2对胃癌细胞中核因子-κ B（NF-κ B）、Snail和E-钙粘蛋白的影响。通过Western blot和实时聚合酶链反应测定基因表达。为了分析NF-.B抑制是否会中断COX-2或前列腺素E2（PGE 2）对E-钙粘蛋白的调节作用，在NF-.B特异性siRNA的存在下，用塞来昔B或前列腺素E2处理胃癌细胞。结果：在mRNA和蛋白水平上，胃癌细胞中的考克斯-2表达水平最高。siRNA下调考克斯-2表达可导致NF-κ B、B和Snail表达减少，而E-cadherin表达增加。siRNA下调NF-.B的表达也导致SGC-7901细胞中E-cadherin和Snail的表达降低。然而，考克斯-2的表达没有改变后，细胞与NF-κ B特异性siRNA处理的SGC-7901细胞。塞来昔布处理胃癌细胞后，Snail表达降低，E-cadherin表达增加。相反，用PGE 2处理SGC-7901细胞导致Snail增加和E-cadherin减少。结论：考克斯-2可能位于NF-κ B的上游，通过NF-κ B/Snail信号通路调控胃癌细胞E-cadherin的表达。(C)2013年百世登。All rights reserved.
AIM: To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E-cadherin in gastric cancer cells.METHODS: COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-kappa B NF-kappa B), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-.B inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-.B specific siRNA.RESULTS: Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-.B and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-.B also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-kappa B specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNAmediated knockdown of NF-kappa B partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.CONCLUSION: COX-2 likely functions upstream of NF kappa B and regulates the expression of E-cadherin via NF kappa B/Snail signaling pathway in gastric cancer cells. (C) 2013 Baishideng. All rights reserved.