The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action

被引:245
作者
Smith, ML [1 ]
Hawcroft, G [1 ]
Hull, MA [1 ]
机构
[1] Univ Leeds, St James Hosp, Mol Med Unit, Leeds LS9 7TF, W Yorkshire, England
关键词
apoptosis; beta-catenin; colorectal cancer; cyclooxygenase; non-steroidal anti-inflammatory drug;
D O I
10.1016/S0959-8049(99)00333-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and induce apoptosis in human colorectal cancer cells in vitro. It remains unclear whether individual NSAIDs act by cyclooxygenase-2 (COX-2) inhibition and how NSAIDs exert their antiproliferative effects. We investigated the effects of NS-398 (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor) and aspirin on four human colorectal cancer cell lines (HT29.Fu, HCA-7, SW480 and HCT116). NS-398 completely inhibited proliferation, induced G1 arrest and promoted apoptosis in COX-2-expressing cells (HT29.Fu and HCA-7). However, indomethacin had similar effects on all cells, regardless of COX-2 expression. NS-398 also had anti-proliferative activity on COX-2-negative cell lines (SW480 and HCT116). Aspirin inhibited proliferation of all cell lines but did not induce apoptosis. Indomethacin decreased beta-catenin protein expression in all cells (unlike NS-398 or aspirin). NSAIDs act on human colorectal cancer cells via different mechanisms. Decreased beta-catenin protein expression may mediate the anti-proliferative effects of indomethacin. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:664 / 674
页数:11
相关论文
共 39 条
[1]   Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells [J].
Brockman, JA ;
Gupta, RA ;
DuBois, RN .
GASTROENTEROLOGY, 1998, 115 (05) :1049-1055
[2]  
CHAPPLE KS, 2000, IN PRESS AM J PATHOL
[3]   UP-REGULATION OF CYCLOOXYGENASE-2 GENE-EXPRESSION IN HUMAN COLORECTAL ADENOMAS AND ADENOCARCINOMAS [J].
EBERHART, CE ;
COFFEY, RJ ;
RADHIKA, A ;
GIARDIELLO, FM ;
FERRENBACH, S ;
DUBOIS, RN .
GASTROENTEROLOGY, 1994, 107 (04) :1183-1188
[4]   Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells [J].
Efstathiou, JA ;
Noda, M ;
Rowan, A ;
Dixon, C ;
Chinery, R ;
Jawhari, A ;
Hattori, T ;
Wright, NA ;
Bodmer, WF ;
Pignatelli, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) :3122-3127
[5]  
Elder DJE, 1997, GASTROENTEROLOGY, V113, P1999
[6]  
Elder DJE, 1997, CLIN CANCER RES, V3, P1679
[7]  
Elder DJE, 1996, CANCER RES, V56, P2273
[8]   NS-398, A NEW ANTIINFLAMMATORY AGENT, SELECTIVELY INHIBITS PROSTAGLANDIN-G/H SYNTHASE CYCLOOXYGENASE (COX-2) ACTIVITY IN-VITRO [J].
FUTAKI, N ;
TAKAHASHI, S ;
YOKOYAMA, M ;
ARAI, I ;
HIGUCHI, S ;
OTOMO, S .
PROSTAGLANDINS, 1994, 47 (01) :55-59
[9]   Meloxicam inhibits the growth of colorectal cancer cells [J].
Goldman, AP ;
Williams, CS ;
Sheng, HM ;
Lamps, LW ;
Williams, VP ;
Pairet, M ;
Morrow, JD ;
DuBois, RN .
CARCINOGENESIS, 1998, 19 (12) :2195-2199
[10]   SODIUM-BUTYRATE INDUCES APOPTOSIS IN HUMAN COLONIC TUMOR-CELL LINES IN A P53-INDEPENDENT PATHWAY - IMPLICATIONS FOR THE POSSIBLE ROLE OF DIETARY FIBER IN THE PREVENTION OF LARGE-BOWEL CANCER [J].
HAGUE, A ;
MANNING, AM ;
HANLON, KA ;
HUSCHTSCHA, LI ;
HART, D ;
PARASKEVA, C .
INTERNATIONAL JOURNAL OF CANCER, 1993, 55 (03) :498-505