Radiosensitivity enhancement by Co-NMS-mediated mitochondrial impairment in glioblastoma.,Journal of Cellular Physiology

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Radiosensitivity enhancement by Co-NMS-mediated mitochondrial impairment in glioblastoma.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-05-11 , DOI: 10.1002/jcp.29774
Yang Liu _{1,

2,

3} , Taofeng Zhang ₄ , Guo Li ₅ , Sirui Li ₅ , Jili Li ₆ , Quanyi Zhao ₆ , Qingfen Wu _{1,

2,

3} , Dan Xu _{1,

2,

3} , Xiaoli Hu _{1,

2,

3} , Luwei Zhang _{1,

2,

3} , Qiang Li _{1,

2,

3} , Hong Zhang _{1,

2,

3} , Bin Liu ₅

Affiliation

We investigated the radiosensitizing effects of Co‐NMS, a derivative of nimesulide based on a cobalt carbonyl complex, on malignant glioma cells. In the zebrafish exposed to Co‐NMS ranging from 5 to 20 μM, cell death and heat shock protein 70 expression in the brain and neurobehavioral performance were evaluated. Our data showed that Co‐NMS at 5 μM did not cause the appreciable neurotoxicity, and thereby was given as a novel radiation sensitizer in further study. In the U251 cells, Co‐NMS combined with irradiation treatment resulted in significant inhibition of cell growth and clonogenic capability as well as remarkable increases of G2/M arrest and apoptotic cell population compared to the irradiation alone treatment. This demonstrated that the Co‐NMS administration exerted a strong potential of sensitizing effect on the irradiated cells. With regard to the tumor radiosensitization of Co‐NMS, it could be primarily attributed to the Co‐NMS‐derived mitochondrial impairment, reflected by the loss of mitochondrial membrane potential, the disruption of mitochondrial fusion and fission balance as well as redox homeostasis. Furthermore, the energy metabolism of the U251 cells was obviously suppressed by cotreatment with Co‐NMS and irradiation through repressing mitochondrial function. Taken together, our findings suggested that Co‐NMS could be a desirable drug to enhance the radiotherapeutic effects in glioblastoma patients.

中文翻译：

Co-NMS介导的胶质母细胞瘤线粒体损伤增强放射敏感性。

我们研究了Co-NMS（一种基于羰基钴复合物的尼美舒利的衍生物）对恶性神经胶质瘤细胞的放射增敏作用。在暴露于5-20μM的Co-NMS的斑马鱼中，评估了细胞死亡和脑中热休克蛋白70的表达以及神经行为表现。我们的数据表明，Co-NMS的浓度为5μM不会引起明显的神经毒性，因此在进一步研究中被认为是一种新型的放射增敏剂。在U251细胞中，与单独照射相比，Co-NMS结合放射处理可显着抑制细胞生长和克隆形成能力，并显着增加G2 / M阻滞和凋亡细胞群。这表明Co-NMS给药对照射的细胞具有很强的增敏作用。关于Co-NMS的肿瘤放射增敏作用，它可能主要归因于Co-NMS衍生的线粒体损伤，反映为线粒体膜电位的丧失，线粒体融合和裂变平衡的破坏以及氧化还原稳态。此外，通过与Co-NMS共同处理和通过抑制线粒体功能进行照射，U251细胞的能量代谢明显受到抑制。综上所述，我们的发现表明，Co-NMS可能是增强胶质母细胞瘤患者放射治疗效果的理想药物。线粒体融合和裂变平衡的破坏以及氧化还原稳态。此外，通过与Co-NMS共同处理和通过抑制线粒体功能进行照射，U251细胞的能量代谢明显受到抑制。综上所述，我们的发现表明，Co-NMS可能是增强胶质母细胞瘤患者放射治疗效果的理想药物。线粒体融合和裂变平衡的破坏以及氧化还原稳态。此外，通过与Co-NMS共同处理和通过抑制线粒体功能进行照射，U251细胞的能量代谢明显受到抑制。综上所述，我们的发现表明，Co-NMS可能是增强胶质母细胞瘤患者放射治疗效果的理想药物。

更新日期：2020-05-11

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