一种选择性环氧化酶-2抑制剂NS-398，通过使细胞周期停滞来抑制人恶性纤维组织细胞瘤细胞系中的细胞生长。

A selective cyclooxygenase-2 inhibitor, NS-398, inhibits cell growth by cell cycle arrest in a human malignant fibrous histiocytoma cell line.

作者信息

Yamashita Hideki, Osaki Mitsuhiko, Honjo Soichiro, Yoshida Haruhiko, Teshima Ryota, Ito Hisao

机构信息

Division of Organ Pathology Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.

出版信息

Anticancer Res. 2003 Nov-Dec;23(6C):4671-6.

PMID:14981912

Abstract

BACKGROUND

NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to suppress cell proliferation and induce apoptosis in a variety of human cancer cell lines in vitro, except for sarcoma cell lines. The aim of this study was to examine the effect of NS-398 on two human malignant fibrous histiocytoma (MFH) cell lines: MFH-ino and MFH-ToE.

MATERIALS AND METHODS

We investigated the effect of NS-398 at various concentrations on the growth of MFH cell lines using cell proliferation assay, cell cycle analysis and EIA assay of PGE2 production.

RESULTS

Western blot analysis revealed COX-2 protein expression in both MFH cell lines. NS-398 at 10 or 100 microM resulted in inhibition of the cell proliferation in a dose- and time-dependent manner. NS-398 at 100 microM also induced G0/G1 arrest accompanied by up-regulation of P21WAF1 in MFH-ino cells in a time-dependent manner until 72 hours. NS-398 slightly increased the number of cells in the G2/M-phase and decreased the number in the G0/G1-phase in MFH-ToE cells lacking p53 gene function. Moreover, NS-398 down-regulated PGE2 production in the MFH-ToE cells in a time-dependent manner, but not in the MFH-ino cells.

CONCLUSION

Our results indicate that NS-398 inhibits the cell growth and induces G0/G1 arrest in MFH-ino cells accompanied with up-regulation of P21WAF1.

摘要

背景

NS - 398是一种选择性环氧化酶 - 2（COX - 2）抑制剂，已显示在体外能抑制多种人类癌细胞系的细胞增殖并诱导凋亡，但肉瘤细胞系除外。本研究的目的是检测NS - 398对两种人类恶性纤维组织细胞瘤（MFH）细胞系：MFH - ino和MFH - ToE的影响。

材料与方法

我们使用细胞增殖测定、细胞周期分析和PGE2产生的酶免疫分析（EIA），研究了不同浓度的NS - 398对MFH细胞系生长的影响。

结果

蛋白质印迹分析显示两种MFH细胞系中均有COX - 2蛋白表达。10或100微摩尔的NS - 398以剂量和时间依赖性方式抑制细胞增殖。100微摩尔的NS - 398还以时间依赖性方式诱导MFH - ino细胞中的G0/G1期阻滞，同时P21WAF1上调，直至72小时。在缺乏p53基因功能的MFH - ToE细胞中，NS - 398使G2/M期细胞数量略有增加，G0/G1期细胞数量减少。此外，NS - 398以时间依赖性方式下调MFH - ToE细胞中的PGE2产生，但在MFH - ino细胞中未下调。