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首页> 外文期刊>Cell biology international. >mGlu3 receptor blockade inhibits proliferation and promotes astrocytic phenotype in glioma stem cells.
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mGlu3 receptor blockade inhibits proliferation and promotes astrocytic phenotype in glioma stem cells.

机译:mGlu3受体阻滞抑制神经胶质瘤干细胞的增殖并促进星形细胞表型。

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We have characterised, using both in vivo and in vitro methods, the effects of the metabotropic glutamate receptor subtype 3 (mGlu3) antagonist (LY341495) and agonist (LY379268) on the proliferation and differentiation of glioma stem cells (GSC). For in vitro studies, a CCK-8 assay was used to determine the cell proliferation, flow cytometry was performed to determine cell cycle phases, and immunohistochemistry and laser confocal microscopy were employed to detect CD133 expression. For in vivo studies, GSCs were injected into nude mice treated with either LY379268 or LY341495 and the growth of the tumours was measured after 3 weeks. When compared with controls, the proliferation rates and proportion of cells in S phase within the LY341495 treated group decreased in a time-dependent manner. In the presence of differentiation medium containing LY341495, GSC differentiation was diverted into an astrocyte rather than neuronal phenotype. The growth rate and volume of tumours injected into nude mice was reduced in LY341495 treated mice compared with controls. Thus pharmacological blockade of mGlu3 receptor signalling pathway significantly inhibits the growth and proliferation of GSCs both in vitro and in vivo while promoting differentiation to astrocytes. These results further implicate mGlu3 in the biology of glioma and as a target for continued research.
机译:我们已经使用体内和体外方法表征了代谢型谷氨酸受体亚型3(mGlu3)拮抗剂(LY341495)和激动剂(LY379268)对神经胶质瘤干细胞(GSC)增殖和分化的影响。对于体外研究,使用CCK-8分析确定细胞增殖,进行流式细胞术确定细胞周期阶段,并使用免疫组织化学和激光共聚焦显微镜检测CD133表达。为了进行体内研究,将GSCs注射入用LY379268或LY341495处理的裸鼠中,并在3周后测量肿瘤的生长。当与对照组比较时,LY341495处理组内S期细胞的增殖速率和比例以时间依赖性方式降低。在含有LY341495的分化培养基的存在下,GSC分化转移到星形胶质细胞而不是神经元表型。与对照组相比,LY341495处理的小鼠中注射到裸鼠中的肿瘤的生长速率和体积降低。因此,mGlu3受体信号传导途径的药理学阻断作用显着抑制了体外和体内GSC的生长和增殖,同时促进了向星形胶质细胞的分化。这些结果进一步暗示了mGlu3在神经胶质瘤的生物学中,并作为继续研究的目标。

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