甘草次酸对K562细胞增殖抑制作用及其机制研究

被引：20

作者：

柯文娟

刘新月

陈燕

舒文秀

机构：

[1] 华中科技大学同济医学院协和医院血液病研究所

来源：

中草药 | 2008年 / 05期

关键词：

甘草次酸; 白血病; 细胞周期; cyclin D1; cyclin E;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

1008 ;

摘要：

目的研究甘草次酸对髓系白血病细胞系K562体外增殖抑制作用,分析其引起细胞周期的变化及探讨其可能的抗癌机制。方法MTT法检测甘草次酸对K562细胞增殖活性的影响;Hoechst 33258染色法观察细胞凋亡形态学改变;流式细胞术分析细胞周期的变化以及cyclin D1和cyclin E蛋白表达的变化;RT-PCR测定细胞中cyclin D1和cyclin E mRNA表达的改变。结果甘草次酸对K562有增殖抑制作用,其抑制作用呈现为量效和时效依赖性,作用48 h的IC50值为(93.1±3.7)μmol/L。甘草次酸可以诱导细胞发生凋亡,Hoechst染色可见细胞核内凋亡小体。甘草次酸可以诱导K562细胞周期阻滞于G0/G1期,同时G2/M期细胞比例减小,S期变化不明显,仅在最大浓度组稍有降低。甘草次酸可以同时下调K562细胞内cylin D1和cyclin E蛋白和基因的表达,下调作用与剂量呈正相关。结论甘草次酸能明显抑制K562细胞增殖,并诱导其周期阻滞于G0/G1期。该效应可能与其下调周期蛋白cyclin D1和cyclin E表达有关,有望成为新型抗肿瘤中药。

引用

页码：714 / 718

页数：5

共 9 条

[1]

Selecti vit y of acti on of gl yc yrrhizi n deri vati ves on t he gro wt h of MCF-7 and HEP-2 cells. Rossi T,Castelli M,Zando meneghi G,et al. Anticancer Research . 2003

[2]

Effect ofglycyrrhizin and its diastereoisomers on the growth of humantumor cells:pre2 liminary finding. Malagoli M,Castelli M,Baggio A,et al. Phytotherapy Research . 1998

[3]

Biotransformation ofglycyrrhizin to 18-beta-glycyrrhetinic acid-3-O-beta-D-glucuronide by Streptococcus LJ-22,a human intestinalbacterium. Kim D H,Lee S W,Han M J,et al. Biological and Pharmaceutical Bulletin . 1999

[4]

Cell proliferation inchildhood acute leukemia.Comparison of Ki267 andproliferating cell nuclear antigen immunocytochemical andDNA flow cytometric analysis. Ito M,Tsurusawa M,Zha Z,et al. Cancer . 1992

[5]

Human cyclin E, a new cyclin that interactswith two members of the CDC2 gene family. Koff A,Cross F,Fisher A,et al. Cell . 1991

[6]

Cyclin E overexpression inrelapsed adult acute lymphoblastic leukemias of B-cell lineage. Scuderi R,Palucka K A,Pokrovskaja K,et al. Blood . 1996

[7]

Human cyclin E, a nuclear protein essential for the G1 to S phase transition. Ohtsubo M,Theodoras A M,Schumacher J,et al. Molecular and Cellular Biology . 1995

[8]

Role of the cyclin-dependent kinase inhibitors in the development of cancer. Hirama T,Koeffler HP. Blood . 1995

[9]

Joining the complex : cyclin2dependent kinase inhibitory proteins and the cell cycle. Peter M,Herskowitz I. Cell . 1994

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