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

Jieyu Zhou, Jiping Ding, Xingkai Ma, Meichao Zhang, Zirong Huo, Yao Yuan, Dong Li, Zhentao Wang

2020OncoTargets and Therapy24 citationsDOIOpen Access PDF

Abstract

Purpose: 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

Topics & Concepts

Nasopharyngeal carcinomaRadioresistanceKEAP1RadiosensitivityCancer researchGene knockdownCell cultureChemistryBiologyRadiation therapyMedicineBiochemistryInternal medicineGeneticsTranscription factorGeneGenomics, phytochemicals, and oxidative stressPhytochemical Studies and BioactivitiesIon Channels and Receptors