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木犀草素A通过抑制Cdk7介导的人胃癌BGC-823细胞中Cdc2/p34的表达诱导G2/M期细胞周期阻滞。

Oroxylin A induces G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells.

作者信息

Yang Yong, Hu Yang, Gu Hong-Yan, Lu Na, Liu Wei, Qi Qi, Zhao Li, Wang Xiao-Tang, You Qi-Dong, Guo Qing-Long

机构信息

Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing 210009, People's Republic of China.

出版信息

J Pharm Pharmacol. 2008 Nov;60(11):1459-63. doi: 10.1211/jpp/60.11.0006.

Abstract

We reported previously that oroxylin A, a natural product isolated from Scutellariae Radix, was a potent apoptosis inducer of human hepatoma HepG2 cells. In this study, cell-cycle arrest of BGC-823 human gastric carcinoma cells caused by oroxylin A has been investigated. Based on our 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometric analysis, treatment of BGC-823 cells with growth suppressive concentrations of oroxylin A caused an irreversible arrest in the G2/M phase of the cell cycle. Western blot analysis demonstrated that oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2). The results suggested that oroxylin A induced G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells.

摘要

我们之前报道过,从黄芩中分离出的天然产物木犀草素A是一种强效的人肝癌HepG2细胞凋亡诱导剂。在本研究中,对木犀草素A引起的人胃癌BGC - 823细胞的细胞周期阻滞进行了研究。基于我们的3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐(MTT)检测和流式细胞术分析,用生长抑制浓度的木犀草素A处理BGC - 823细胞会导致细胞周期在G2/M期出现不可逆的阻滞。蛋白质免疫印迹分析表明,木犀草素A诱导的BGC - 823细胞周期阻滞与细胞周期蛋白依赖性激酶2/周期蛋白依赖激酶4(cdc2/p34)、细胞周期蛋白B1和细胞周期蛋白A表达的显著降低有关。此外,用木犀草素A处理的细胞降低了细胞周期蛋白依赖性激酶7(Cdk7)的表达,而Cdk7负责M期促进因子(细胞周期蛋白B1/Cdc2)的低表达。结果表明,木犀草素A通过抑制人胃癌BGC - 823细胞中Cdk7介导的Cdc2/p34表达来诱导G2/M期细胞周期阻滞。

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