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瑞因通过抑制 ERK 诱导人源和鼠源神经胶质瘤细胞凋亡和自噬并介导细胞分化。

Rhein induces apoptosis and autophagy in human and rat glioma cells and mediates cell differentiation by ERK inhibition.

机构信息

Department of Neurosurgery, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.

出版信息

Microb Pathog. 2017 Dec;113:168-175. doi: 10.1016/j.micpath.2017.10.031. Epub 2017 Oct 19.

DOI:10.1016/j.micpath.2017.10.031
PMID:29056497
Abstract

In this study, we investigated the anticancer potentials of Rhein, an anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98 glioma cells. The experimental studies revealed that Rhein induced cell cycle arrest, caspase mediated apoptosis. It results in the formation of intracellular acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable cells towards elongation of matured astrocytes was proved by monitoring dramatic changes in morphological characteristics as well as identified from the elevation of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not alter the phosphorylated MAPKs activation including p-38, JNK and NF-κB, transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98 glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein effects on morphology and expressions of GFAP but did not help to induce any apoptosis or autophagy. Collective data exhibited that potentials of rhein in anti-cancer property in ERK-independent apoptosis and autophagy in association with downregulated ERK-dependent differentiation process of glioma cell lines.

摘要

在这项研究中,我们调查了大黄素的抗癌潜力,大黄素是最常用的中国大黄的蒽醌衍生物,对大鼠 F98 神经胶质瘤细胞有影响。实验研究表明,大黄素诱导细胞周期停滞,半胱天冬酶介导的细胞凋亡。它导致细胞质中细胞内酸性囊泡的形成,导致自噬。通过监测形态特征的显著变化以及鉴定神经胶质纤维酸性蛋白 (GFAP) 表达的升高,证明存活细胞向成熟星形胶质细胞的分化。大黄素处理不会改变包括 p-38、JNK 和 NF-κB 在内的磷酸化 MAPKs 的激活,转录单位,而大黄素显著抑制 F98 神经胶质瘤细胞中 ERK1/2 的激活。PD98059 是一种特异性的 ERK 激活抑制剂,它模拟了大黄素对形态和 GFAP 表达的影响,但不能诱导任何细胞凋亡或自噬。总的来说,数据表明大黄素在与下调 ERK 依赖性分化过程相关的非 ERK 依赖性细胞凋亡和自噬中具有抗癌特性。

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