Depletion of SLC7A11 Sensitizes Nasopharyngeal Carcinoma Cells to Ionizing Radiation.

IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2024-01-01 DOI:10.2174/0109298665308572240513113105
Fan Yang, Hongxun Gong, Shiyan Chen, Jianzhong Li, Ning Huang, Maoxin Wang
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Abstract

Background: 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.

Objective: 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.

Methods: 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 Fe2+, 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.

Results: 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 Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR.

Conclusion: 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.

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消耗 SLC7A11 可使鼻咽癌细胞对电离辐射敏感
背景:放疗是鼻咽癌(NPC)的主要治疗方法。然而,由于放射抗药性的存在,放疗的疗效大打折扣。铁突变是电离辐射(IR)诱导的一种新型铁依赖性细胞死亡调节机制,在促进癌细胞死亡方面发挥着作用。然而,人们对铁突变的增强与鼻咽癌细胞对 IR 敏感性增加之间的关系仍知之甚少:本研究旨在探讨红外辐射与鼻咽癌铁突变之间的关系,以及铁突变抑制因子 SLC7A11 在红外辐射处理的鼻咽癌细胞中的作用:方法:对 CNE1 和 HNE-2 NPC 细胞进行 IR 处理。方法:CNE1和HNE-2鼻咽癌细胞均接受了IR处理,我们采用qPCR和Western印迹法评估了对照组和IR处理组鼻咽癌细胞中铁突变相关基因的表达。此外,我们还使用 MTT 法检测了这些 NPC 细胞的存活率。我们采用 JC-1 和 DCFH-DA 染色法评估对照组和经 IR 处理的鼻咽癌细胞的线粒体膜电位和活性氧(ROS)水平。此外,我们还检测了这些细胞中Fe2+、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,我们还删除了经 IR 处理的鼻咽癌细胞中的 SLC7A11,以研究其对这些细胞铁变态反应的影响:结果:在 CNE1 和 HNE-2 细胞中,IR 上调了铁氧化相关基因的表达,包括 SLC7A11、ACSL4、COX2、FTH1 和 GPX4。红外处理还导致细胞活力下降、线粒体膜电位紊乱、ROS 水平升高、谷胱甘肽水平改变和 Fe2+ 水平升高。敲除 SLC7A11 可增强鼻咽癌细胞对 IR 的敏感性:结论:红外线可诱导鼻咽癌细胞的铁变态反应,刺激铁变态反应有可能成为一种治疗策略,以提高红外线治疗鼻咽癌患者的疗效。
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来源期刊
Protein and Peptide Letters
Protein and Peptide Letters 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
98
审稿时长
2 months
期刊介绍: Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis
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