首页> 外文期刊>CNS neuroscience & therapeutics. >Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH / GLI 1 Signaling Pathway iin Vitro/i and iVivo/i
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Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH / GLI 1 Signaling Pathway iin Vitro/i and iVivo/i

机译:姜黄素通过抑制SHH / GLI 1信号通路体外和 Vivo 抑制恶性胶质瘤细胞的生长并诱导凋亡。

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Summary Aims To study the role of curcumin on glioma cells via the SHH / GLI 1 pathway in vitro and vivo . Methods The effects of curcumin on proliferation, migration, apoptosis, SHH / GLI 1 signaling, and GLI 1 target genes expression were evaluated in multiple glioma cell lines in vitro . A U87‐implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI 1. Results Curcumin showed cytotoxic effects on glioma cell lines in vitro . Both mRNA and protein levels of SHH / GLI 1 signaling ( S hh, S mo, GLI 1) were downregulated in a dose‐ and time‐dependent manner. Several GLI 1‐dependent target genes ( C yclin D 1, B cl‐2, F oxm1) were also downregulated. Curcumin treatment prevented GLI 1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of B ax to B cl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI 1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group. Conclusion This study shows that curcumin holds a great promise for SHH / GLI 1 targeted therapy against gliomas.
机译:总结目的研究姜黄素通过SHH / GLI 1途径在体内和体外对胶质瘤细胞的作用。方法测定姜黄素对多种神经胶质瘤细胞株增殖,迁移,凋亡,SHH / GLI 1信号传导和GLI 1靶基因表达的影响。用植入U87的裸鼠模型研究姜黄素对肿瘤体积的作用和GLI 1的抑制作用。结果姜黄素对神经胶质瘤细胞系具有细胞毒性作用。 SHH / GLI 1信号的mRNA和蛋白水平(S hh,S mo,GLI 1)均以剂量和时间依赖性方式下调。几个GLI 1依赖性靶基因(C yclin D 1,B cl-2,F oxm1)也被下调。姜黄素处理可防止GLI 1转运进入细胞核并降低其报告基因的浓度。姜黄素抑制细胞增殖,集落形成,迁移和诱导凋亡,其在Bax与Bcl2之比增加后部分通过线粒体途径介导。与对照组相比,体内腹膜内注射姜黄素可减少肿瘤体积,GLI 1表达,阳性染色细胞数量并延长生存期。结论这项研究表明姜黄素有望在SHH / GLI 1靶向治疗神经胶质瘤中具有广阔的前景。

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