Reinema F V, Kaanders J H A M, Peeters W J M, Adema G J, Sweep F C G J, Bussink J, Span P N
Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Clin Transl Radiat Oncol. 2024 Jan 11;45:100726. doi: 10.1016/j.ctro.2024.100726. eCollection 2024 Mar.
Radiotherapy (RT) is a mainstay component of treatment for patients with head and neck squamous cell carcinoma (HNSCC), but responses vary. As RT relies upon oxidative damage, antioxidant expression in response to RT-induced reactive oxygen species (ROS) could compromise treatment response. We aimed to examine local and systemic antioxidant responses to increased RT-induced ROS in relation to treatment success.
Nuclear factor erythroid 2-related factor 2 (NRF2), the main antioxidant transcription factor, was immunofluorescently stained in FaDu cells and in tumor biopsies of patients with oral cavity/oropharynx HNSCC before and after five fractions of RT. Besides, total antioxidant capacity (TAC) was analyzed in HNSCC tumor cells and in serum of HNSCC patients before, during, and after RT.
Data revealed an increase in NRF2 expression and TAC in head and neck cancer cells over the course of 5 daily fractions of 2 Gy. In accordance, also in patients' tumors NRF2 expression increased, which was associated with increased serum TAC during RT. Increasing serum TAC was related to impaired local tumor control.
Radiation induced NRF2 expression and upregulated TAC, which may compromise the effect of RT-induced ROS. Changes in serum TAC during RT could serve as a novel predictor of treatment outcome in HNSCC patients.Medical Ethics Review Committee (CMO) approval - CMO number: 2007/104.
放射治疗（RT）是头颈部鳞状细胞癌（HNSCC）患者治疗的主要组成部分，但疗效各异。由于放疗依赖氧化损伤，对放疗诱导的活性氧（ROS）产生反应的抗氧化剂表达可能会损害治疗效果。我们旨在研究局部和全身抗氧化反应与放疗诱导的ROS增加之间的关系，以及与治疗成功的关系。
主要抗氧化转录因子核因子红细胞2相关因子2（NRF2）在FaDu细胞以及口腔/口咽HNSCC患者放疗五疗程前后的肿瘤活检组织中进行免疫荧光染色。此外，在放疗前、放疗期间和放疗后，对HNSCC肿瘤细胞和HNSCC患者血清中的总抗氧化能力（TAC）进行分析。
数据显示，在每天2 Gy共5个疗程的放疗过程中，头颈部癌细胞中NRF2表达和TAC增加。同样，在患者肿瘤中NRF2表达也增加，这与放疗期间血清TAC增加有关。血清TAC增加与局部肿瘤控制受损有关。
放疗诱导NRF2表达并上调TAC，这可能会损害放疗诱导的ROS的作用。放疗期间血清TAC的变化可作为HNSCC患者治疗结果的新预测指标。医学伦理审查委员会（CMO）批准 - CMO编号：2007/104。
