[丙戊酸对Kasumi-1细胞系细胞周期的抑制作用及其机制]

[Inhibitory effect of valproic acid on cell cycle of Kasumi-1 cell line and its mechanism].

作者信息

Zhao Lei, Zhang Zhi-Hua, Zhu Cui-Min

机构信息

Department of Hematology, Affiliated Hospital of Chengde Medical College, Chengde 067000, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2008 Dec;29(12):802-5.

PMID:19176032

Abstract

OBJECTIVE

To investigate the influence of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on cell cycle of Kasumi-1 cells, and explore its molecular mechanism.

METHODS

Kasumi-1 cells were treated with VPA at different concentration and different time cell cycle changes were analyzed by flow cytometry. Cyclin D1 and p21(WAF1/CIP) gene, a cyclin-dependent kinase inhibitor, were determined by semi-quantitative RT-PCR and Western blot.

RESULTS

(1) VPA blocked the Kasumi-1 cells in G(0)/G(1) phase. (2) Compared with control group, 3 mmol/L VPA treated Kasumi-1 cells for different times caused their mRNA expression of cyclin D1 decreased. Treated with VPA at different concentration for 3 days, the mRNA expression decreased in a dose-dependent manner. (3) VPA induced p21(WAF1/CIP) mRNA expression increased in a time- and dose-dependent manner. The p21(WAF1/CIP) protein increased with increasing concentration of VPA at day 3. The p21(WAF1/CIP) protein significantly increased with 3 mmol/L VPA treatment for 2 d (2.498 +/- 0.240).

CONCLUSION

VPA can arrest Kasumi-1 cell in G(0)/G(1) phase through the regulation of cyclin D1 and p21(WAF1/CIP).

摘要

目的

研究组蛋白去乙酰化酶（HDAC）抑制剂丙戊酸（VPA）对Kasumi-1细胞周期的影响，并探讨其分子机制。

方法

用不同浓度的VPA处理Kasumi-1细胞，不同时间后通过流式细胞术分析细胞周期变化。采用半定量RT-PCR和蛋白质免疫印迹法检测细胞周期蛋白D1（Cyclin D1）及细胞周期蛋白依赖性激酶抑制剂p21（WAF1/CIP）基因的表达。

结果

（1）VPA使Kasumi-1细胞阻滞于G(0)/G(1)期。（2）与对照组相比，3 mmol/L VPA处理不同时间的Kasumi-1细胞，其Cyclin D1的mRNA表达降低。不同浓度VPA处理3天，其mRNA表达呈剂量依赖性降低。（3）VPA诱导p21（WAF1/CIP）的mRNA表达呈时间和剂量依赖性增加。第3天，p21（WAF1/CIP）蛋白随VPA浓度增加而增加。3 mmol/L VPA处理2天，p21（WAF1/CIP）蛋白显著增加（2.498±0.240）。