COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells

被引：25

作者：

Choi, EM

Kwak, SJ

Kim, YM

Ha, KS

Kim, JI

Lee, SW

Han, JA ^{[1
]}

机构：

[1] Kangwon Natl Univ, Coll Med, Dept Biochem & Mol Biol, Chunchon 200701, South Korea

[2] Dankook Univ, Coll Med, Dept Biochem, Cheonan 330714, South Korea

[3] Hallym Univ, Coll Med, Dept Biochem, Chunchon 200702, South Korea

[4] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[5] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

来源：

EXPERIMENTAL AND MOLECULAR MEDICINE | 2005年 / 37卷 / 03期

关键词：

anoikis; bladder; cancer; COX-2; Mcl-1; Pl-3K/Akt;

D O I：

10.1038/emm.2005.27

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoilkis by a PI-3K inhibitor, LY294002. Furthermore, COX-2 enhanced Mcl-1 expression in the anoilkis process, implying that Mcl-1 also may be involved in mediating the survival function of COX-2. Together, these results suggest that COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway and probably by enhancement of Mcl-1 expression in human bladder cancer cells. This antianoikis effect of COX-2 may be a part of mechanisms to promote tumor development and progression.

引用

页码：199 / 203

页数：5

共 22 条

[1] Cyclooxygenase 2 promotes cell survival by stimulation of dynein light chain expression and inhibition of neuronal nitric oxide synthase activity [J].