Yang Fan, Gong Hongxun, Chen Shiyan, Li Jianzhong, Huang Ning, Wang Maoxin
Department of Otorhinolaryngology - Head and Neck, Fuzong Clinical College of Fujian Medical University, the 900th Hospital of Joint Logistic Support Force of PLA, Fuzhou 350025, China.
Protein Pept Lett. 2024;31(4):323-331. doi: 10.2174/0109298665308572240513113105.
Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood.
This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells.
CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells.
IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR.
IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.
放射治疗是鼻咽癌（NPC）的主要治疗选择。然而，由于放射抗性，其疗效受到影响。铁死亡是一种由电离辐射（IR）诱导的新型铁依赖性调节性细胞死亡，在促进癌细胞死亡中起作用。然而，增强的铁死亡与NPC细胞对IR敏感性增加之间的关系仍知之甚少。
本研究旨在探讨IR与NPC中铁死亡之间的关联，以及铁死亡抑制因子SLC7A11在IR处理的NPC细胞中的作用。
对CNE1和HNE-2 NPC细胞进行IR处理。我们进行qPCR和蛋白质印迹以评估对照和IR处理的NPC细胞中铁死亡相关基因的表达。此外，我们使用MTT法测量这些NPC细胞的活力。采用JC-1和DCFH-DA染色评估对照和IR处理的NPC细胞中的线粒体膜电位和活性氧（ROS）水平。此外，我们检测了这些细胞中Fe、丙二醛（MDA）、还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）的水平。此外，我们在IR处理的NPC细胞中敲低SLC7A11以研究其对这些细胞铁死亡的影响。
IR上调了CNE1和HNE-2细胞中铁死亡相关基因的表达，包括SLC7A11、ACSL4、COX2、FTH1和GPX4。IR处理还导致细胞活力降低、线粒体膜电位破坏、ROS水平升高、谷胱甘肽水平改变和Fe水平升高。敲低SLC7A11增强了NPC细胞对IR的敏感性。
IR可能诱导NPC细胞发生铁死亡，刺激铁死亡可能作为一种治疗策略来提高IR治疗NPC患者的疗效。
