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

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

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作者:Yu Yan #, Ying-Ying Cheng #, Yan-Ru Li #, Xu-Wen Jiao, Yin-Ming Liu, Hai-Yan Cai, Yin-Xiu Ding

Abstract

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.

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