G3BP1 Depletion Increases Radiosensitisation by Inducing Oxidative Stress in Response to DNA Damage

Anticancer Res. 2019 Nov;39(11):6087-6095. doi: 10.21873/anticanres.13816.

Abstract

Background: RAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules. Many functions related to the survival and progression of cancer have been reported. The current study aimed to investigate the role of G3BP1 in radio-sensitisation of cancer cells.

Materials and methods: Radiation sensitivity and chemosensitivity were analysed in A549 and H460 cells transfected with G3BP1 siRNAs, and N-acetyl-L-cysteine (NAC) was used to elucidate the involvement of reactive oxygen species (ROS).

Results: G3BP1 depletion sensitised lung cancer cell lines to radiation, and the effect was related to ROS. G3BP1 depletion impaired the intracellular ROS scavenging system and NAC abolished the radiation-sensitive phenotypes caused by G3BP1 depletion.

Conclusion: The study suggested G3BP1 as a promising target for radio- and chemosensitisation of lung cancer.

Keywords: G3BP1; chemo-sensitization; non-small cell lung cancer; radio-sensitisation; reactive oxygen species.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cell Proliferation
  • DNA Damage / radiation effects*
  • DNA Helicases / antagonists & inhibitors*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Doxorubicin / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects*
  • Poly-ADP-Ribose Binding Proteins / antagonists & inhibitors*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • RNA Helicases / antagonists & inhibitors*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Recognition Motif Proteins / antagonists & inhibitors*
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism
  • RNA, Small Interfering / genetics
  • Radiation Tolerance / drug effects*
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Biomarkers, Tumor
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Doxorubicin
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases