NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines

被引:66
作者
Cheng, JD [1 ]
Imanishi, H
Amuro, Y
Hada, T
机构
[1] Hyogo Med Univ, Div Hepatobiliary & Pancreat Dis, Dept Internal Med, Nishinomiya, Hyogo 663, Japan
[2] Shantou Univ, Coll Med, Tumor Inst, Guangdong, Peoples R China
关键词
selective COX-2 inhibitor; cell growth; cell cycle; hepatocellular carcinoma cells;
D O I
10.1002/ijc.10409
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time- and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX-2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS-398 in hepatocellular carcinoma cell lines. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:755 / 761
页数:7
相关论文
共 30 条
[1]  
Bae SH, 2001, CLIN CANCER RES, V7, P1410
[2]   EXISTENCE OF 2 POPULATIONS OF CYCLIN PROLIFERATING CELL NUCLEAR ANTIGEN DURING THE CELL-CYCLE - ASSOCIATION WITH DNA-REPLICATION SITES [J].
BRAVO, R ;
MACDONALDBRAVO, H .
JOURNAL OF CELL BIOLOGY, 1987, 105 (04) :1549-1554
[3]   Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis [J].
Chan, TA ;
Morin, PJ ;
Vogelstein, B ;
Kinzler, KW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :681-686
[4]  
DOUGLAS JEE, 1997, CLIN CANCER RES, V3, P1679
[5]  
DOUGLAS JEE, 2000, INT J CANCER, V86, P553
[6]   Sulindac sulfide inhibits Ras signaling [J].
Herrmann, C ;
Block, C ;
Geisen, C ;
Haas, K ;
Weber, C ;
Winde, G ;
Möröy, T ;
Müller, O .
ONCOGENE, 1998, 17 (14) :1769-1776
[7]   HUMAN CYCLOOXYGENASE-2 CDNA [J].
HLA, T ;
NEILSON, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) :7384-7388
[8]   Evidence for involvement of yeast proliferating cell nuclear antigen in DNA mismatch repair [J].
Johnson, RE ;
Kovvali, GK ;
Guzder, SN ;
Amin, NS ;
Holm, C ;
Habraken, Y ;
Sung, P ;
Prakash, L ;
Prakash, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (45) :27987-27990
[9]   PCNA: Structure, functions and interactions [J].
Kelman, Z .
ONCOGENE, 1997, 14 (06) :629-640
[10]   Expression of cyclooxygenase-2 in human hepatocellular carcinoma: Relevance to tumor dedifferentiation [J].
Koga, H ;
Sakisaka, S ;
Ohishi, M ;
Kawaguchi, T ;
Taniguchi, E ;
Sasatomi, K ;
Harada, M ;
Kusaba, T ;
Tanaka, M ;
Kimura, R ;
Nakashima, Y ;
Nakashima, O ;
Kojiro, M ;
Kurohiji, T ;
Sata, M .
HEPATOLOGY, 1999, 29 (03) :688-696