OncoTargets and Therapy (2020-09-01)

The NRF2/KEAP1 Pathway Modulates Nasopharyngeal Carcinoma Cell Radiosensitivity via ROS Elimination

  • Zhou J,
  • Ding J,
  • Ma X,
  • Zhang M,
  • Huo Z,
  • Yao Y,
  • Li D,
  • Wang Z

Journal volume & issue
Vol. Volume 13
pp. 9113 – 9122

Abstract

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Jieyu Zhou,1,* Jiping Ding,2,* Xingkai Ma,3,* Meichao Zhang,2 Zirong Huo,1 Yuan Yao,2 Dong Li,2 Zhentao Wang1 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, People’s Republic of China; 2Department of Radiation Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Otolaryngology, Zhangjiagang First People’s Hospital, Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong Li; Zhentao Wang Email [email protected]; [email protected]: Radioresistance is a vital obstacle for the prognosis of human nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. Here, we explored the role of the NRF2/KEAP1 pathway in radioresistance of NPC cell lines.Materials and Methods: We selected NPC cell lines CNE-1 and CNE-2, treated them with ionization, and subsequently determined the levels of NRF2, KEAP1, antioxidant enzymes, and ROS. We then evaluated the effect of NRF2 or KEAP1 inhibition on cell proliferation, colony formation, and radiosensitivity in CNE2 cells.Results: We discovered that the NRF2/KEAP1 signaling pathway can be activated by radiotherapy in NPC cells, while NRF2 knockdown enhances the sensitivity of CNE-2 cells to radiation treatment. In contrast, the silencing of KEAP1 inhibits the sensitivity of CNE-2 cells to radiation treatment.Conclusion: Our results suggest that NRF2/KEAP1 signaling may serve as an essential regulator of the radioresistance of NPC and may be applied as a novel therapeutic approach for the sensitization of NPC to radiation.Keywords: nasopharyngeal carcinoma, NRF2, KEAP1, radiosensitivity

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