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麻风树素通过下调NF-κB和上调凋亡抑制因子来抑制胶质瘤细胞活力。

Inhibition of glioma cell viability by jatrophone via NF-κB down-regulation and apoptosis inhibitor up-regulation.

作者信息

Yuan Lei, Wang Fei, Zhang Ting, Zhang Yiming, Pan Hong, Lv Guoguang, Zhang Baozhong

机构信息

Postgraduate Training Base of Rocket Army Special Medical Center of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.

Department of Neurosurgery, Rocket Army Medical Center, Beijing, China.

出版信息

Arch Med Sci. 2020 Apr 15;21(1):224-232. doi: 10.5114/aoms.2020.94439. eCollection 2025.

Abstract

INTRODUCTION

The present study evaluated the pro-survival signaling pathway inhibition potential of jatrophone in glioblastoma cells with the intention to develop effective treatment for glioblastoma.

MATERIAL AND METHODS

Changes in proliferation of cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes were evaluated by electron microscopy and apoptosis by flow cytometry.

RESULTS

The proliferative potential of glioma cells showed significant reduction on treatment with jatrophone. The shrinkage and detachment from the flask surface was prominent in glioma cells on treatment with 15 µM jatrophone. Treatment with jatrophone (4.8 µM) for 72 h increased apoptosis in U87MG and A172 cells. The immunocytochemistry showed a significant decrease in the level of intracellular NF-κB p65 in glioma cells on treatment with jatrophone. Jatrophone treatment significantly suppressed nuclear NF-κB p65/total NF-κB p65 in glioma cells. Treatment with jatrophone suppressed levels of survivin, XIAP and Bcl-2 in glioma cells relative to control. The Bax level in glioma cells was enhanced markedly relative to control on treatment with jatrophone. Activation of caspase-9 and -3 in glioma cells was markedly increased on treatment with jatrophone.

CONCLUSIONS

Jatrophone acts as inhibitory agent for glioblastoma cell proliferation and mediator of apoptosis. Therefore, jatrophone can be used as a therapeutic agent for glioblastoma treatment.

摘要

引言

本研究评估了麻风树素对胶质母细胞瘤细胞促生存信号通路的抑制潜力,旨在开发针对胶质母细胞瘤的有效治疗方法。

材料与方法

通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法检测细胞增殖变化。通过电子显微镜评估形态学变化,通过流式细胞术评估细胞凋亡。

结果

用麻风树素处理后,胶质瘤细胞的增殖潜力显著降低。用15µM麻风树素处理后,胶质瘤细胞从培养瓶表面收缩和脱离的现象明显。用4.8µM麻风树素处理72小时可增加U87MG和A172细胞的凋亡。免疫细胞化学显示,用麻风树素处理后,胶质瘤细胞内NF-κB p65水平显著降低。麻风树素处理显著抑制了胶质瘤细胞中核NF-κB p65/总NF-κB p65。与对照组相比,用麻风树素处理可抑制胶质瘤细胞中生存素、XIAP和Bcl-2的水平。与对照组相比,用麻风树素处理后,胶质瘤细胞中Bax水平显著升高。用麻风树素处理后,胶质瘤细胞中caspase-9和-3的激活明显增加。

结论

麻风树素可作为胶质母细胞瘤细胞增殖的抑制剂和凋亡的介导剂。因此,麻风树素可作为治疗胶质母细胞瘤的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1065/11969555/ea022c26a223/AMS-21-1-118396-g001.jpg

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