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引用次数: 0
摘要
本研究旨在探讨转铁蛋白受体(TFR1)在非小细胞肺癌(NSCLC)中的潜在分子机制。采用苏木精-伊红(HE)染色进行组织学分析。CD8+T细胞的数量通过流式细胞术和免疫荧光测定法确定。蛋白表达用 Western 印迹法检测。碘化丙啶(PI)染色检测铁变态反应。异种移植实验用于确定肿瘤的生长情况。结果表明,干扰素(IFN)-γ加右旋糖酐铁(FeDx)可诱导NSCLC细胞铁超载和铁突变。此外,IFN-γ介导的TFR1上调通过阻断铁蛋白重链1(FTH1)/铁蛋白轻链(FTL)信号传导,促进了铁蛋白吞噬和肿瘤细胞的铁嗜性。然而,TFR1基因敲除抑制了肿瘤细胞的铁突变。此外,FeDx介导的铁过载会提高抗程序性死亡配体1(PD-L1)疗法的敏感性。临床上,TFR1在NSCLC患者中被下调。低水平的TFR1预示着CD8+ T细胞的减少。综上所述,IFN-γ与铁代谢疗法相结合可能会为NSCLC提供一种新的替代疗法。
TFR1-Mediated Iron Metabolism Orchestrates Tumor Ferroptosis and Immunity in Non-Small Cell Lung Cancer.
This study aimed to investigate the underlying molecular mechanisms of transferrin receptor (TFR1) in non-small cell lung cancer (NSCLC). Histological analysis was performed using hematoxylin-eosin (HE) staining. The number of CD8+ T cell were determined by flow cytometry and immunofluorescence assays. mRNA levels were analyzed by qRT-PCR. Protein expression was detected by western blot. Ferroptosis was detected by using propidium iodide (PI) staining. Xenograft experiment was applied for determining tumor growth. The results showed that interferon (IFN)-γ plus iron dextran (FeDx) induced iron overload and the ferroptosis of NSCLC cells. Moreover, IFN-γ-mediated upregulation of TFR1 promoted ferritinophagy and tumor cell ferroptosis via blocking via blocking ferritin heavy chain 1 (FTH1)/ ferritin light chain (FTL) signaling. However, TFR1 knockout suppressed the ferroptosis of tumor cells. Furthermore, FeDx-mediated iron overload promoted the sensitivity of anti-programmed death ligand 1 (PD-L1) therapies. Clinically, TFR1 was downregulated in NSCLC patients. Low levels of TFR1 predicted decreased CD8+ T cells. Taken together, IFN-γ combined with iron metabolism therapies may provide a novel alternative for NSCLC.
期刊介绍:
The Journal of Nuclear Science and Technology (JNST) publishes internationally peer-reviewed papers that contribute to the exchange of research, ideas and developments in the field of nuclear science and technology, to contribute peaceful and sustainable development of the World.
JNST ’s broad scope covers a wide range of topics within its subject category, including but are not limited to:
General Issues related to Nuclear Power Utilization: Philosophy and Ethics, Justice and Policy, International Relation, Economical and Sociological Aspects, Environmental Aspects, Education, Documentation and Database, Nuclear Non-Proliferation, Safeguard
Radiation, Accelerator and Beam Technologies: Nuclear Physics, Nuclear Reaction for Engineering, Nuclear Data Measurement and Evaluation, Integral Verification/Validation and Benchmark on Nuclear Data, Radiation Behaviors and Shielding, Radiation Physics, Radiation Detection and Measurement, Accelerator and Beam Technology, Synchrotron Radiation, Medical Reactor and Accelerator, Neutron Source, Neutron Technology
Nuclear Reactor Physics: Reactor Physics Experiments, Reactor Neutronics Design and Evaluation, Reactor Analysis, Neutron Transport Calculation, Reactor Dynamics Experiment, Nuclear Criticality Safety, Fuel Burnup and Nuclear Transmutation,
Reactor Instrumentation and Control, Human-Machine System: Reactor Instrumentation and Control System, Human Factor, Control Room and Operator Interface Design, Remote Control, Robotics, Image Processing
Thermal Hydraulics: Thermal Hydraulic Experiment and Analysis, Thermal Hydraulic Design, Thermal Hydraulics of Single/Two/Multi Phase Flow, Interactive Phenomena with Fluid, Measurement Technology...etc.