NS398 对胰腺癌细胞周期及其蛋白依赖性激酶抑制物p21Wafl/cipl、p27Kipl/pic2的影响

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (1): 38-42.

NS398 对胰腺癌细胞周期及其蛋白依赖性激酶抑制物p21^Wafl/cipl、p27^Kipl/pic2的影响

陈其奎¹, 韩际奥², 陈锦武¹, 黄志清¹, 朱兆华¹

¹浙中山大学附属第二医院消化内科, 广州 510120, 广东;
²河南省郑州市第五人民医院消化内科, 郑州 100089, 河南

收稿日期:2006-08-01 修回日期:2006-10-05 出版日期:2007-01-26 发布日期:2020-10-26
通讯作者: 陈其奎, 男, 博士, 教授, 博士生导师, 研究方向:胰腺癌的诊断和治疗。Tel:020-81332598 　E-mail: qkchen@21cn.com
基金资助:
广东省自然科学基金项目(984211)

Effects of NS398 on cell cycle and related cyclin-dependent kinase inhibitors p21^waf1/cip1 and p27^kip1/pic2 in human pancreatic carcinoma cells

CHEN Qi-kui¹, HAN Ji-ao², CHEN Jing-wu¹, HUANG Zhi-qing¹, ZHU Zhao-hua¹

¹Department of Gastroenterology, the Second Affilated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China;
²Department of Gastroenterology, the Fifth Hospital of Zhengzhou City, Zhengzhou 100089, Henan, China

Received:2006-08-01 Revised:2006-10-05 Online:2007-01-26 Published:2020-10-26

摘要/Abstract

摘要： 目的: 观察选择性环氧合酶-2(COX-2) 抑制剂NS398 对胰腺癌细胞周期及细胞周期相关蛋白p21^Wafl/cipl 、p27^Kipl/pic2转录和表达的影响, 探讨NS398 的抗胰腺癌机制。方法: 以NS398 和前列腺素E2(PGE2) 处理SW1990 人胰腺癌细胞, 分别采用MTT法检测细胞活力, 酶联免疫分析法(ELISA) 检测细胞内PGE2 含量, 流式细胞仪(FCM) 检测细胞周期变化, 并以半定量逆转录聚合酶链式反应(RT-PCR) 和Western 印迹检测COX-2 及细胞周期相关蛋白p21^Wafl/cipl 、p27^Kipl/pic2的mRNA 和蛋白水平。结果: NS398 抑制胰腺癌细胞生长, 并呈剂量依赖性减少细胞内PGE2 的生成;NS398 诱导细胞周期相关蛋白p21^Wafl/cipl 和p27^Kipl/pic2 转录和表达的升高并诱导部分细胞阻滞在G0 G1 期(较对照组升高11 %);10 nmol/L 的外源性PGE2 可增加胰腺癌细胞的活力, 但并不能拮抗NS398 对细胞活力的抑制作用或细胞周期分布的改变, 以及COX-2 、p21^Wafl/cipl 、p27^Kipl/pic2 的转录和表达。结论: NS398 可能通过增强p21^Wafl/cipl 和p27^Kipl/pic2的表达而诱导细胞周期的阻滞, 从而抑制胰腺癌细胞的生长活力。但NS398 并非通过抑制COX-2 的唯一机制, 还可能存在其它非COX-2途径。

关键词: 胰腺肿瘤, NS398, 环氧合酶, 前列腺素E₂, 细胞周期

Abstract: AIM: To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor, NS398, on cell cycle and related cyclin-dependent kinase inhibitors p21^waf1/cip1 and p27^kip1/pic2 in human pancreatic carcinoma cells. METHODS: SW1990 human pancreatic carcinoma cells were treated with NS398 (100 μmol/L), prostaglandin E2 (PGE2, 10 nmol/L) and their combination, respectively.The inhibitory effects of NS398 on SW1990 cell were detected by using MTT assay.The cell cycle was measured with flow cytometry.The level of intracellular PGE2 was determined with ELISA.The mRNA of p21^waf1/cip1and p27^kip1/pic2was detected by semi-quantitative RT-PCR.The expression of p21^waf1/cip1 and p27^kip1/pic2 protein was detected by Western blotting analysis. RESULTS: NS398 inhibited the growth of SW1990 cell and decreased level of intracellular PGE2 in a dose-dependent manner.NS398 caused cell accumulation in G0 G1 phase that was 11 % higher than control.The mRNA and protein of p21^waf1/cip1and p27^kip1/pic2were up-regulated by NS398.PGE2 stimulated cell growth, but factorial experiment showed that 10 nmol/L of PGE2 could not antagonize inhibitory effects of cell growth, cell cycle distribution, transcription and expression of COX-2, p21^waf1/cip1 and p27^kip1/pic2 induced by NS398 in SW1990 cells. CONCLUSION: The results suggest that selective COX-2 inhibitor, NS398, can induce inhibitory effects of cell growth and G0 G1 cell cycle arrest in SW1990 cells by upregulation of p21^waf1/cip1 and p27^kip1/pic2 and may be not dependent of PGE2 pathway.

Key words: pancreatic neoplasms, NS398, cyclooxygenase, prostaglandin E₂, cell cycle

中图分类号:

R965.2
R966

陈其奎, 韩际奥, 陈锦武, 黄志清, 朱兆华. NS398 对胰腺癌细胞周期及其蛋白依赖性激酶抑制物p21^Wafl/cipl、p27^Kipl/pic2的影响[J]. 中国临床药理学与治疗学, 2007, 12(1): 38-42.

CHEN Qi-kui, HAN Ji-ao, CHEN Jing-wu, HUANG Zhi-qing, ZHU Zhao-hua. Effects of NS398 on cell cycle and related cyclin-dependent kinase inhibitors p21^waf1/cip1 and p27^kip1/pic2 in human pancreatic carcinoma cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(1): 38-42.

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