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Inhibitor of Wnt receptor 1 suppresses the effects of Wnt1, Wnt3a and β‑catenin on the proliferation and migration of C6 GSCs induced by low‑dose radiation.
Oncology Reports ( IF 4.2 ) Pub Date : 2023-12-15 , DOI: 10.3892/or.2023.8681
Yu Yan 1 , Ying-Ying Cheng 2 , Yan-Ru Li 1 , Xu-Wen Jiao 1 , Yin-Ming Liu 1 , Hai-Yan Cai 3 , Yin-Xiu Ding 1
Affiliation  

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 in vitro 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‑H2AX 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.

中文翻译:


Wnt 受体 1 抑制剂可抑制 Wnt1、Wnt3a 和 β-catenin 对低剂量辐射诱导的 C6 GSC 增殖和迁移的影响。



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,在直线加速器下,通过流式细胞术分析、免疫细胞化学和蛋白质印迹分析检查0.3和3.0 Gy低剂量辐射(LDR)对体外C6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胶质瘤干细胞的增殖,这是通过增强的Wnt/β-连环蛋白信号介导的,即与神经胶质瘤的侵袭性有关。 LDR 处理增加了 DNA 损伤标记 γ-H 2 AX 的表达,但促进了细胞存活,并显着减少了凋亡和坏死细胞。当 LDR 细胞也用 Wnt 受体 1 (IWR1) 抑制剂处理时,细胞增殖和迁移显着减少。 IWR1 处理显着抑制 Wnt1、Wnt3a 和 β-catenin 蛋白表达。总的来说,目前的结果表明,IWR1 治疗有效地使神经胶质瘤干细胞放射增敏,并有助于克服 LDR 所带来的生存优势,这对放射抗性神经胶质瘤的靶向治疗具有重要意义。
更新日期:2023-12-15
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