Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak

被引:114
作者
Zhou, XM
Wong, BCY [1 ]
Fan, XM
Zhang, HB
Lin, MCM
Kung, HF
Fan, DM
Lam, SK
机构
[1] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China
[3] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian, Peoples R China
关键词
D O I
10.1093/carcin/22.9.1393
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.
引用
收藏
页码:1393 / 1397
页数:5
相关论文
共 36 条
[1]   Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis - Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells [J].
Boulares, AH ;
Yakovlev, AG ;
Ivanova, V ;
Stoica, BA ;
Wang, GP ;
Iyer, S ;
Smulson, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (33) :22932-22940
[2]  
Coogan PF, 2000, CANCER EPIDEM BIOMAR, V9, P119
[3]   Inhibition of caspase-3-mediated poly(ADP-ribose) polymerase (PARP) apoptotic cleavage by human PARP autoantibodies and effect on cells undergoing apoptosis [J].
Decker, P ;
Isenberg, D ;
Muller, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) :9043-9046
[4]   POLY(ADP-RIBOSE) POLYMERASE - A MOLECULAR NICK-SENSOR [J].
DEMURCIA, G ;
DEMURCIA, JM .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (04) :172-176
[5]   Expression and regulation of Bcl-2, Bcl-xl, and Bax correlate with p53 status and sensitivity to apoptosis in childhood acute lymphoblastic leukemia [J].
Findley, HW ;
Gu, LB ;
Yeager, AM ;
Zhou, MX .
BLOOD, 1997, 89 (08) :2986-2993
[6]   P53, MDM-2, BAX and BCL-2 and drug resistance in chronic lymphocytic leukemia [J].
Johnston, JB ;
Daeninck, P ;
Verburg, L ;
Lee, K ;
Williams, G ;
Israels, LG ;
Mowat, MRA ;
Begleiter, A .
LEUKEMIA & LYMPHOMA, 1997, 26 (5-6) :435-+
[7]  
Kim R, 1999, INT J ONCOL, V15, P751
[8]  
Kondo S, 2000, CANCER RES, V60, P4328
[9]   Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database [J].
Langman, MJS ;
Cheng, KK ;
Gilman, EA ;
Lancashire, RJ .
BRITISH MEDICAL JOURNAL, 2000, 320 (7250) :1642-1646
[10]  
LAUWERS GY, 1995, CANCER, V75, P2209, DOI 10.1002/1097-0142(19950501)75:9<2209::AID-CNCR2820750904>3.0.CO