Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3β/NAG-1 pathway
Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3β/NAG-1 pathway
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DOI：
10.1016/j.canlet.2006.11.032
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发表时间：
2007-06-28
期刊：
影响因子：
9.7
通讯作者：
Hu, Pin-Jin
中科院分区：
文献类型：
--
作者：
Pang, Rul-Ping;Zhou, Jia-Guo;Hu, Pin-Jin
本研究旨在探讨塞来昔布对考克斯-2缺陷型胃癌细胞株MGC-803凋亡的作用机制。我们发现塞来昔布处理诱导MGC-803细胞凋亡的半胱天冬酶依赖。塞来昔布抑制Ser 473 Akt和Scr 9 GSK 3 β磷酸化，并诱导非甾体抗炎药激活基因-1（NAG-1）表达上调。塞来昔布对NAG-I表达的影响可通过GSK 3 β抑制剂SB 216763预处理而消除。此外，通过siRNA沉默GSK 3 β基因抑制塞来昔布诱导的NAG-I表达。我们的研究表明Akt/GSK 3 β/NAG-1信号通路可能是塞来昔布对胃癌细胞的考克斯-2非依赖性作用的主要机制。(C)2006爱思唯尔爱尔兰有限公司保留所有权利。
In this study, we analyzed the mechanisms of the apoptotic effects of celecoxib on COX-2 deficient gastric cancer cell line, MGC-803. We found celecoxib treatment induced caspase-dependent apoptosis in MGC-803 cells. Celecoxib inhibited Ser473 Akt and Scr9 GSK3 beta phosphorylation and induced upregulation of nonsteroidal anti-inflammatory drugs-activated gene-1 (NAG-1) expression. The effects of celecoxib on NAG-I expression were abolished by pretreatment with GSK3 beta inhibitor, SB216763. Furthermore, GSK3 beta gene silencing by siRNA inhibited the celecoxib-induced NAG-I expression. Our study demonstrated that Akt/GSK3 beta/NAG-1 signal pathway may represent as the major mechanism of the COX-2-independent effects of celecoxib on gastric cancer cells. (C) 2006 Elsevier Ireland Ltd. All rights reserved.