生物学杂志

生物学杂志 ›› 2024, Vol. 41 ›› Issue (6): 20-.doi: 10.3969/j.issn.2095-1736.2024.06.020

• 研究报告 • 上一篇    下一篇

抑制GS活性增强放疗诱导的胶质瘤细胞铁死亡

卢益军1,2， 周　臣2， 钱俊超1,2   

  1. 1. 中国科学技术大学 研究生院科学岛分院， 合肥 230026；
    2. 中国科学院合肥物质科学研究院， 合肥 230031
  • 出版日期:2024-12-18 发布日期:2024-12-16
  • 通讯作者: 钱俊超，博士，研究员，研究方向为肿瘤发病机理及诊疗研究，E-mail:qianjunchao@hmfl.ac.cn
  • 作者简介:卢益军，硕士，研究方向为肿瘤生物学，E-mail:luyijun@mail.ustc.edu.cn
  • 基金资助:
    国家自然科学基金资助项目（U1932158， 81871085，82271519）； 山东省自然科学基金肿瘤防治联合基金重点项目(ZR2019LZL018）； 安徽省自然科学基金杰出青年项目（2208085J10）； 中国博士后科学基金面上项目（2019M652403）； 山东省博士后创新项目（202002048）

Inhibition of glutamine synthetase in glioma cells enhances radiotherapy-induced ferroptosis #br#

LU Yijun1,2, ZHOU Chen2, QIAN Junchao1,2   

  1. 1. Science Island Branch, Graduate School of USTC, Hefei 230026, China;
    2. Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
  • Online:2024-12-18 Published:2024-12-16

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摘要： 研究旨在探究谷氨酰胺合成酶（glutamine synthetase， GS）在放疗诱导的胶质瘤细胞铁死亡过程中的作用。使用GS活性抑制剂（L-蛋氨酸亚砜亚胺，MSO）和电离辐射（IR）处理GL261细胞。DCFH-DA荧光探针和谷胱甘肽（GSH）试剂盒用于检测活性氧（ROS）水平和GSH含量，C11-BODIPY 581/591荧光探针和实时荧光定量PCR用于检测脂质过氧化和PTGS2的表达，CCK8用于评估细胞增殖率和存活率。利用小鼠胶质瘤原位模型研究MSO和放疗对胶质瘤生长的作用。结果显示，抑制GS活性促进放疗后细胞ROS的产生和GSH耗竭，增强脂质过氧化，上调PTGS2的表达，并显著抑制细胞增殖率和存活率。动物实验中，MSO和放疗的联合治疗相较传统放疗具有更强的肿瘤抑制效果。结果表明，抑制GS可以显著增强放疗对胶质瘤细胞的铁死亡诱导作用，提高肿瘤放疗敏感性，为临床治疗提供新的策略与靶点。

关键词: 脑胶质瘤, 谷氨酰胺合成酶, L-蛋氨酸亚砜亚胺, 放疗, 铁死亡

Abstract: The study aims to investigate the role of glutamine synthetase (GS) in radiotherapy-induced ferroptosis in glioma. The glioma cells GL261 were treated using Ionizing radiation (IR) and GS inhibitor (L-methionine sulfoximine, MSO). The levels of reactive oxygen species (ROS) was detected with the DCFH-DA fluorescent probe. The changes in glutathione (GSH) content were measured using a GSH assay kit. Cellular lipid peroxidation levels were investigated with the C11-BODIPY 581/591 fluorescent probe. The expression of the ferroptosis marker PTGS2 was detected by RT-qPCR. Cell proliferation rate and cell viability were assessed using CCK-8 assay. The effects of MSO and RT on growth inhibition of tumors were further investigate by establishing murine orthotopic glioma model. The results showed that inhibiting the activity of GS promoted the production of ROS and GSH depletion in cells after radiotherapy, enhanced lipid peroxidation, up-regulated the expression of PTGS2, and significantly inhibited cell proliferation and viability. Animal experiments confirmed that the combination of MSO and radiotherapy showed a stronger tumor suppression effect compared to conventional radiotherapy. In conclusion, inhibiting glutamine synthetase can significantly enhance the induction of ferroptosis in glioma cells by radiotherapy. This approach increases the sensitivity of tumor cells to radiotherapy and provides new strategies and targets for clinical treatment.

Key words: glioma, glutamine synthetase, L-methionine sulfoximine；radiotherapy, ferroptosis

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