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胶质母细胞瘤中胶质瘤干细胞与非干细胞样细胞之间Nrf2表达的差异

Differential Nrf2 expression between glioma stem cells and non-stem-like cells in glioblastoma.

作者信息

Zhu Jianhong, Wang Handong, Ji Xiangjun, Zhu Lin, Sun Qing, Cong Zixiang, Zhou Yuan, Liu Huandong, Zhou Mengliang

机构信息

Department of Neurosurgery, Jinling Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu 210089, P.R. China.

Department of Neurosurgery, Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, Nanjing, Jiangsu 210002, P.R. China.

出版信息

Oncol Lett. 2014 Mar;7(3):693-698. doi: 10.3892/ol.2013.1760. Epub 2013 Dec 16.

Abstract

Glioblastoma multiforme (GBM), the most commonly occurring primary intracranial tumor, is associated with a negative outcome, regardless of the availability of multimodal therapies. However, the identification of glioma stem cells (GSCs), which are small groups of cells within the GBM, has resulted in novel avenues for research. GSCs are resistant to numerous types of environmental stress, such as irradiation, antitumor drugs and hypoxia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a significant role the cellular response to oxidative stress and previous studies have supported the significance of Nrf2 in GBM; however, the role of Nrf2 in GSCs remains unclear. In the present study, Nrf2 in CD133 GBM cells and CD133 GSCs from GBM were compared. GSCs from GBM, which express the surface marker CD133, were separated by magnetic cell sorting and analyzed by immunofluorescence in 24-well clusters and cell counting using flow cytometry. The expression of Nrf2 was detected at the transcriptional and translational levels in CD133 and CD133 cells, and the result indicated that GSCs were successfully isolated from the GBM. The percentage of tumor stem cells in total cells was between 0.49 and 0.91%. Nrf2 was overexpressed in CD133 GSCs when compared with CD133 GBM cells, which indicated that the expression of Nrf2 in GSCs was closely correlated with malignant proliferation and differentiation of the GBM. Therefore, it was concluded that Nrf2 may be a potential biomarker and rational therapeutic target in GBM.

摘要

多形性胶质母细胞瘤(GBM)是最常见的原发性颅内肿瘤,无论多模态治疗方法是否可用,其预后都很差。然而,胶质瘤干细胞(GSCs)的发现为研究开辟了新途径,胶质瘤干细胞是GBM中的一小群细胞。GSCs对多种环境应激具有抗性,如辐射、抗肿瘤药物和缺氧。核因子红细胞2相关因子2(Nrf2)在细胞对氧化应激的反应中起重要作用,先前的研究支持Nrf2在GBM中的重要性;然而,Nrf2在GSCs中的作用仍不清楚。在本研究中,对来自GBM的CD133 GBM细胞和CD133 GSCs中的Nrf2进行了比较。通过磁珠细胞分选法分离出表达表面标志物CD133的GBM来源的GSCs,并在24孔板中进行免疫荧光分析,同时使用流式细胞术进行细胞计数。检测了CD133和CD133细胞中Nrf2在转录和翻译水平的表达,结果表明成功从GBM中分离出了GSCs。肿瘤干细胞在总细胞中的比例为0.49%至0.91%。与CD133 GBM细胞相比,CD133 GSCs中Nrf2过表达,这表明GSCs中Nrf2的表达与GBM的恶性增殖和分化密切相关。因此,得出结论,Nrf2可能是GBM中一个潜在的生物标志物和合理的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b0/3919893/d63f61b1faa3/OL-07-03-0693-g00.jpg

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