VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor

Genro Kashino1, Shinko Kobashigawa2, Aoki Uchikoshi2

  • 1Radioisotope Research Center, Nara Medical University, Shijo-Machi, Kashihara, Japan. kashino@naramed-u.ac.jp.

Insights

Vascular endothelial growth factor (VEGF) protects cells from radiation by reducing oxidative stress and altering mitochondrial function. This effect on cell survival is independent of DNA double-strand break induction.

Area of Science:

  • Cellular biology
  • Radiation oncology
  • Molecular medicine

Background:

  • Vascular endothelial growth factor (VEGF) is crucial for angiogenesis and a target in anticancer therapies.
  • The role of VEGF in cellular response to ionizing radiation, particularly concerning cell-cell communication and radiosensitivity, remains unclear.

Purpose of the Study:

  • To investigate the influence of VEGF on the radiosensitivity of cells.
  • To elucidate the underlying mechanisms of VEGF's effect on cellular response to ionizing radiation.

Main Methods:

  • Cultured rat C6 glioma cells were treated with recombinant VEGF (rVEGF) or endogenous VEGF.
  • Cells were subjected to X-ray irradiation.
  • Radiosensitivity, oxidative stress levels, DNA double-strand breaks (DSB), and mitochondrial oxygen consumption rate (OCR) were assessed.

Main Results:

  • Recombinant and endogenous VEGF exhibited radioprotective effects on C6 glioma cells against X-ray irradiation.
  • VEGF treatment reduced oxidative stress and decreased mitochondrial oxygen consumption rate (OCR).
  • VEGF did not affect the number of DNA double-strand breaks (DSB) immediately after irradiation.

Conclusions:

  • VEGF enhances cell survival after irradiation by modulating oxidative conditions via mitochondrial function.
  • The radioprotective mechanism of VEGF is independent of its effect on the induction of DNA double-strand breaks.

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