期刊
EUROPEAN JOURNAL OF CANCER
卷 42, 期 3, 页码 422-426出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2005.11.009
关键词
colorectal cancer; celecoxib; COX-2; cell cycle; p53; p21
类别
A unique in vitro system has been developed in our lab that consists of normal enterocytes derived from the rat ileum (IEC-18 cells) and their transformed derivatives with c-K-ras (R1 cells), anti-sense bak (B3 cells) and cyclin D1 (D1 cells). R1 and B3 cells express high level of COX-2 protein and PGE(2). IEC 18 and D1 cells express negligible amount of COX-2, and produce very low level of PGE(2). A relatively low dose of celecoxib (5-10 mu M) induced G(2)/M arrest, followed by induction of apoptosis in the transformed but not in the normal cells. Down-regulation of cyclin B1 and up-regulation of p21 expressions independent of p53 might have cause this cell cycle block. Growth inhibition was related to COX-2 function with 90-95% reduction in PGE(2) production. These findings may be of clinical importance, since low concentration of celecoxib can be achieved in human serum following standard anti-inflammatory (100-200 mg bid) regime. (C) 2005 Elsevier Ltd. All rights reserved.
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