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

Jieyu Zhou1, Jiping Ding2, Xingkai Ma3

  • 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.

Oncotargets and Therapy
|September 28, 2020
PubMed
Abstract

Insights

The NRF2/KEAP1 pathway regulates radioresistance in nasopharyngeal carcinoma (NPC). Inhibiting NRF2 increases sensitivity to radiation, while inhibiting KEAP1 decreases it, offering potential therapeutic targets for NPC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Nasopharyngeal carcinoma (NPC) poses a significant challenge due to radioresistance.
  • The molecular mechanisms underlying NPC radioresistance remain largely unexplored.

Purpose of the Study:

  • To investigate the role of the Nuclear factor erythroid 2-related factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway in NPC radioresistance.
  • To explore potential therapeutic strategies targeting this pathway for improved NPC treatment outcomes.

Main Methods:

  • Utilized NPC cell lines (CNE-1, CNE-2) and subjected them to ionizing radiation.
  • Assessed NRF2, KEAP1, antioxidant enzyme levels, and reactive oxygen species (ROS) production.
  • Evaluated the impact of NRF2 or KEAP1 inhibition on NPC cell proliferation, colony formation, and radiosensitivity.

Main Results:

  • Radiotherapy activates the NRF2/KEAP1 signaling pathway in NPC cells.
  • NRF2 knockdown significantly enhances CNE-2 cell sensitivity to radiation.
  • KEAP1 silencing reduces CNE-2 cell sensitivity to radiation treatment.

Conclusions:

  • The NRF2/KEAP1 pathway is a critical regulator of radioresistance in NPC.
  • Targeting the NRF2/KEAP1 pathway presents a promising novel therapeutic strategy for sensitizing NPC to radiation therapy.
Keywords:
KEAP1NRF2nasopharyngeal carcinomaradiosensitivity

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