Curcumin increases efficiency of γ-irradiation in gliomas by inhibiting Hedgehog signaling pathway
Curcumin increases efficiency of γ-irradiation in gliomas by inhibiting Hedgehog signaling pathway
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姜黄素通过抑制 Hedgehog 信号通路提高神经胶质瘤 γ 照射的效率
DOI：
10.1080/15384101.2017.1320000
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Jiang, Chuanlu
中科院分区：
文献类型：
--
作者：
Meng, Xiangqi;Cai, Jinquan;Jiang, Chuanlu
据报道，伽马射线照射对神经胶质瘤细胞的治疗效果存在争议。我们的目的是研究伽马射线照射对神经胶质瘤细胞的细胞毒性作用，并探索挽救剩余细胞表型改变的治疗方法。我们采用Transwell实验检测胶质瘤细胞的侵袭和迁移能力。分别采用CCK-8法和流式细胞术检测细胞增殖和凋亡。 Western Blot检测Hedgehog信号通路活性和上皮间质转化（EMT）状态。伽玛射线在体外对 LN229 细胞显示出细胞毒性作用，而这种作用在 U251 细胞中有限。然而，它可以显着刺激 LN229 和 U251 中的 EMT 过程。姜黄素（CCM）可以通过抑制 Gli1 和上调 Sufu 来挽救伽马射线照射诱导的 EMT 过程。 EMT标记物的位置和表达也通过免疫荧光验证。对裸鼠颅内胶质瘤组织进行免疫组织化学检测。联合治疗抑制了细胞迁移和侵袭的能力。这项研究表明，姜黄素可以通过抑制 Hedgehog 信号通路来挽救伽玛射线照射诱导的 EMT 过程，并增强体内和体外的细胞毒作用。
It was reported that gamma-irradiation had a controversial therapeutic effect on glioma cells. We aimed to investigate the cytotoxic effect on the glioma cells induced by gamma-irradiation and explore the treatment to rescue the phenotype alteration of remaining cells. We used transwell assay to detect the glioma cell invasion and migration capacity. Cell proliferation and apoptosis were tested by the CCK-8 assay and flow cytometry respectively. Western Blot was used to detect the activity of Hedgehog signaling pathway and Epithelial-to-Mesenchymal Transition (EMT) status. gamma-irradiation showed cytotoxic effect on LN229 cells in vitro, whereas this contribution was limited in U251 cells. However, it could significantly stimulated EMT process in both LN229 and U251. Curcumin (CCM) could rescue EMT process induced by gamma-irradiation via the suppression of Gli1 and the upregulation of Sufu. The location and expression of EMT markers were also verified by Immunofluorescence. Immunohistochemistry assay was used on intracranial glioma tissues of nude mice. The capacities of cell migration and invasion were suppressed with combined therapy. This research showed Curcumin could rescue the EMT process induced by gamma-irradiation via inhibiting the Hedgehog signaling pathway and potentiate the cell cytotoxic effect in vivo and in vitro.