Abstract
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.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank Professor Hiroki Kuniyasu, Dr. Rina Fujiwara-Tani and Dr. Shiori Mori (Department of Molecular Pathology, Nara Medical University School of Medicine) for their support in using the extracellular flux analyzer. This work was supported by JSPS Grants-in-Aid for Scientific Research (KAKENHI) (Grant numbers JP18K07764, JP26461863 and JP21K07736).
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Kashino wrote the main manuscript text. Kashino and Uchikoshi prepared figure 1, Kashino and Kobashigawa prepared figure 2 and 4, Kashino and Tamari prepared figure 3, and Kashino prepared figure 5. All authors reviewed the manuscript.
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Kashino, G., Kobashigawa, S., Uchikoshi, A. et al. VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor. Radiat Environ Biophys 62, 213–220 (2023). https://doi.org/10.1007/s00411-023-01021-8
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DOI: https://doi.org/10.1007/s00411-023-01021-8