Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Autoimmunity. 2023 Dec;56(1):2234101. doi: 10.1080/08916934.2023.2234101.
Glioblastoma is the most common glioma with high mortality and poor prognosis. Radiation resistance is one of the large challenges in the treatment of glioma. The study aimed to identify whether DNA polymerase ζ affects glioma cell radiosensitivity. The mRNA and protein levels of REV3L and REV7 were examined using quantitative real-time PCR and western blot. After REV3L and REV7 knockdown in a GBM cell line (A172), we assessed cell viability, colonies, apoptosis, and immune escape. The underlying mechanisms were evaluated using western blot and were confirmed using rescue experiments. The results showed that REV3L and REV7 levels were increased in glioma and related to poor survival. γ-ray treatment inhibited cell viability, survival fraction, and immune escape, and induced apoptosis of glioma cells from a GBM cell line, whereas knockdown of REV3L or REV7 enhanced these effects. Mechanically, silencing of REV3L or REV7 inactivated the PI3K/AKT/mTOR pathway. IGF-1 treatment abrogated the effects on cell viability, colonies, and apoptosis induced by REV3L or REV7 knocking down. Taken together, silencing of REV3L and REV7 inhibited radiation resistance inactivating the PI3K/AKT/mTOR pathway, suggesting that targeting DNA polymerase ζ may be a new strategy to reduce the radiotherapy resistance of glioma.
胶质母细胞瘤是最常见的神经胶质瘤，死亡率和预后不良。放射抵抗是神经胶质瘤治疗的一大挑战。本研究旨在确定 DNA 聚合酶 ζ 是否影响神经胶质瘤细胞的放射敏感性。使用实时定量 PCR 和 Western blot 检测 REV3L 和 REV7 的 mRNA 和蛋白水平。在 GBM 细胞系（A172）中敲低 REV3L 和 REV7 后，评估细胞活力、集落形成、细胞凋亡和免疫逃逸。使用 Western blot 评估潜在机制，并通过挽救实验进行验证。结果表明，REV3L 和 REV7 水平在神经胶质瘤中升高，与生存不良有关。γ射线处理抑制细胞活力、存活分数和免疫逃逸，并诱导来自 GBM 细胞系的神经胶质瘤细胞凋亡，而敲低 REV3L 或 REV7 增强了这些效应。机制上，沉默 REV3L 或 REV7 使 PI3K/AKT/mTOR 通路失活。IGF-1 处理消除了 REV3L 或 REV7 敲低诱导的细胞活力、集落形成和细胞凋亡的影响。综上所述，沉默 REV3L 和 REV7 抑制了放射抵抗，使 PI3K/AKT/mTOR 通路失活，表明靶向 DNA 聚合酶 ζ 可能是减少神经胶质瘤放疗抵抗的新策略。
