a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
b Chinese Glioma Cooperative Group (CGCG) , Beijing , China.
Cell Cycle. 2017 Jun 18;16(12):1181-1192. doi: 10.1080/15384101.2017.1320000. Epub 2017 May 2.
It was reported that γ-irradiation had a controversial therapeutic effect on glioma cells. We aimed to investigate the cytotoxic effect on the glioma cells induced by γ-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. γ-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 γ-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 γ-irradiation via inhibiting the Hedgehog signaling pathway and potentiate the cell cytotoxic effect in vivo and in vitro.
有报道称，γ 射线照射对神经胶质瘤细胞具有争议的治疗作用。本研究旨在探讨γ 射线照射对神经胶质瘤细胞的细胞毒性作用，并探索治疗方法以挽救剩余细胞表型改变。我们使用 Transwell 实验检测神经胶质瘤细胞的侵袭和迁移能力。通过 CCK-8 实验和流式细胞术分别检测细胞增殖和凋亡。Western blot 用于检测 Hedgehog 信号通路的活性和上皮间质转化（EMT）状态。γ 射线照射在体外对 LN229 细胞具有细胞毒性作用，而对 U251 细胞的这种作用有限。然而，它可以显著刺激 LN229 和 U251 中 EMT 过程。姜黄素（CCM）通过抑制 Gli1 和 Sufu 的上调，可以挽救 γ 射线照射诱导的 EMT 过程。免疫荧光也验证了 EMT 标志物的位置和表达。免疫组织化学实验用于裸鼠颅内胶质瘤组织。联合治疗可抑制细胞迁移和侵袭能力。本研究表明，姜黄素通过抑制 Hedgehog 信号通路可以挽救 γ 射线照射诱导的 EMT 过程，并增强体内和体外的细胞毒性作用。
