NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, Jilin 130000, P.R. China.
Department of Occupational and Environmental Health, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Int J Mol Med. 2022 May;49(5). doi: 10.3892/ijmm.2022.5121. Epub 2022 Mar 16.
Radiotherapy is an essential and effective treatment modality for cancer. Excessive levels of reactive oxygen species (ROS) induced by ionizing radiation disrupt the redox homeostasis and lead to oxidative stress that may result in cell death. However, the tumor cell microenvironment is dynamic and responds to radiotherapy by activating numerous cellular signaling pathways. By scavenging excess ROS, the activity levels of the endogenous antioxidant enzymes result in radioresistance and worsen the clinical outcomes. To assess the full potential of radiotherapy, it is essential to explore the underlying mechanisms of oxidative stress in radiotherapy for potential target identification. The present review article summarized recent data demonstrating nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) as a powerful transcription factor and one of the major cellular defense mechanisms that protect against oxidative stress in response to radiotherapy; the glutathione (GSH) and thioredoxin (Trx) systems complement each other and are effective antioxidant mechanisms associated with the protection of cancer cells from radiation damage. In addition, it is suggested that dual targeting to inhibit GSH and Trx enzymes may be a potential strategy for the development of radiosensitive and radioprotective drugs.
放射治疗是癌症的一种重要且有效的治疗方式。电离辐射诱导的活性氧（ROS）水平过高会破坏氧化还原平衡，导致氧化应激，从而可能导致细胞死亡。然而，肿瘤细胞微环境是动态的，并通过激活许多细胞信号通路来对放射治疗做出反应。通过清除过多的 ROS，内源性抗氧化酶的活性水平会导致放射抵抗，从而恶化临床结局。为了充分发挥放射治疗的潜力，有必要探讨放射治疗中氧化应激的潜在机制，以确定潜在的治疗靶点。本文综述了最近的数据，这些数据表明核因子红细胞 2 相关因子 2（Nrf2）作为一种强大的转录因子和主要的细胞防御机制之一，可抵御放射治疗引起的氧化应激；谷胱甘肽（GSH）和硫氧还蛋白（Trx）系统相互补充，是与保护癌细胞免受辐射损伤相关的有效抗氧化机制。此外，抑制 GSH 和 Trx 酶的双重靶向可能是开发放射敏感和放射保护药物的潜在策略。
