VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor
VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor
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DOI：
10.1007/s00411-023-01021-8
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发表时间：
2023-03-20
影响因子：
1.7
通讯作者：
Tamari，Yuki
中科院分区：
文献类型：
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作者：
Kashino，Genro;Kobashigawa，Shinko;Tamari，Yuki
血管内皮生长因子（VEGF）与血管生成密切相关。通过抑制VEGF信号进行抗癌治疗已经得到了很好的证实。然而，在电离辐射反应过程中，VEGF在细胞间通讯中的作用尚不清楚。在这里，我们研究了VEGF对细胞放射敏感性的作用。重组血管内皮生长因子（rVEGF）对培养的大鼠C6胶质瘤细胞具有x射线辐射保护作用，并能降低氧化应激。内源性VEGF在C6胶质瘤细胞上清液中也观察到这些作用。VEGF减少氧化应激被认为是辐射防护作用的基础。vegf诱导的氧化应激减少的机制是通过降低线粒体的耗氧量（OCR）来表明的。然而，辐照后立即发生的DNA双链断裂（DSB）数量并未因VEGF治疗而减少。这些结果表明，VEGF通过线粒体功能控制氧化条件，在辐照后细胞存活中发挥作用，而线粒体功能与DSB诱导的效率无关。
Vascular endothelial growth factor (VEGF) is closely related to angiogenesis. Anticancer therapy by inhibiting VEGF signaling is well established. However, the role of VEGF in cell–cell communication during the response to ionizing radiation is not well understood. Here, we examined the role of VEGF on radiosensitivity of cells. The addition of recombinant VEGF (rVEGF) on cultured rat C6 glioma cells showed a radioprotective effects on X-ray irradiation and reduced oxidative stress. These effects were also observed by endogenous VEGF in supernatant of C6 glioma cells. Reduction of oxidative stress by VEGF is suggested to underlie the radioprotective effects. The mechanism of VEGF-induced reduction of oxidative stress was indicated by a decreased oxygen consumption rate (OCR) in mitochondria. However, the number of DNA double-strand breaks (DSB) immediately after irradiation was not reduced by the treatment with VEGF. These results suggest that VEGF plays a role in cell survival after irradiation by controlling the oxidative condition through mitochondrial function that is independent of the efficiency of DSB induction.