Department of Human Anatomy, Basic Medical College, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750006, P.R. China.
The Second Affiliated Hospital of Xi'an Medical University Xi'an, Shaanxi 710038, P.R. China.
Oncol Rep. 2024 Feb;51(2). doi: 10.3892/or.2023.8681. Epub 2023 Dec 15.
The radioresistance of glioma is an important cause of treatment failure and tumor aggressiveness. In the present study, under performed with linear accelerator, the effects of 0.3 and 3.0 Gy low‑dose radiation (LDR) on the proliferation and migration of C6 glioma stem cells were examined by flow cytometric analysis, immunocytochemistry and western blot analysis. It was found that low‑dose ionizing radiation (0.3 Gy) stimulated the proliferation and migration of these cells, while 3.0 Gy ionizing radiation inhibited the proliferation of C6 glioma stem cells, which was mediated through enhanced Wnt/β‑catenin signaling, which is associated with glioma tumor aggressiveness. LDR treatment increased the expression of the DNA damage marker γ‑HAX but promoted cell survival with a significant reduction in apoptotic and necrotic cells. When LDR cells were also treated with an inhibitor of Wnt receptor 1 (IWR1), cell proliferation and migration were significantly reduced. IWR1 treatment significantly inhibited Wnt1, Wnt3a and β‑catenin protein expression. Collectively, the current results demonstrated that IWR1 treatment effectively radio‑sensitizes glioma stem cells and helps to overcome the survival advantages promoted by LDR, which has significant implications for targeted treatment in radioresistant gliomas.
脑胶质瘤的放射抵抗是治疗失败和肿瘤侵袭性的重要原因。在本研究中,采用直线加速器进行低剂量照射(LDR),通过流式细胞术分析、免疫细胞化学和 Western blot 分析,研究了 0.3 和 3.0 Gy 低剂量辐射(LDR)对 C6 神经胶质瘤干细胞增殖和迁移的影响。结果发现,低剂量电离辐射(0.3 Gy)刺激这些细胞的增殖和迁移,而 3.0 Gy 电离辐射抑制 C6 神经胶质瘤干细胞的增殖,这是通过增强 Wnt/β-连环蛋白信号转导介导的,与神经胶质瘤肿瘤侵袭性有关。LDR 处理增加了 DNA 损伤标志物 γ-HAX 的表达,但促进了细胞存活,凋亡和坏死细胞明显减少。当 LDR 细胞也用 Wnt 受体 1(IWR1)抑制剂处理时,细胞增殖和迁移明显减少。IWR1 处理显著抑制 Wnt1、Wnt3a 和 β-连环蛋白蛋白表达。总之,目前的结果表明,IWR1 治疗可有效放射增敏神经胶质瘤干细胞,并有助于克服 LDR 促进的生存优势,这对放射抵抗性神经胶质瘤的靶向治疗具有重要意义。
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