COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells.
- Author:
Eun Mi CHOI
1
;
Sahng June KWAK
;
Young Myeong KIM
;
Kwon Soo HA
;
Jong Il KIM
;
Sam W LEE
;
Jeong A HAN
Author Information
1. Department of Biochemistry and Molecular Biology Kangwon National University College of Medicine Chuncheon 200-701, Korea. gshja@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
anoikis;
bladder;
cancer;
COX-2;
Mcl-1;
PI-3K/Akt
- MeSH:
1-Phosphatidylinositol 3-Kinase/*metabolism;
Anoikis/*physiology;
Bladder Neoplasms/*metabolism/pathology;
Enzyme Activation;
Humans;
Neoplasm Proteins/*metabolism;
Prostaglandin-Endoperoxide Synthase/*metabolism;
Protein-Serine-Threonine Kinases/*metabolism;
Proto-Oncogene Proteins/*metabolism;
Proto-Oncogene Proteins c-bcl-2/*metabolism;
Research Support, Non-U.S. Gov't;
Signal Transduction;
Transfection;
Tumor Cells, Cultured
- From:Experimental & Molecular Medicine
2005;37(3):199-203
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 anoikis by a PI-3K inhibitor, LY294002. Furthermore, COX-2 enhanced Mcl-1 expression in the anoikis 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 anti- anoikis effect of COX-2 may be a part of mechanisms to promote tumor development and progression.
