转铁蛋白受体
癌症研究
碘化丙啶
铁蛋白
生物
流式细胞术
下调和上调
细胞凋亡
细胞
程序性细胞死亡
化学
分子生物学
生物化学
基因
作者
Zunqiao Wang,Xiaoguang Yao,Keping Wang,Bin Wang
出处
期刊:Journal of Environmental Pathology Toxicology and Oncology
[Begell House Inc.]
日期:2023-08-23
卷期号:43 (2): 1-12
被引量:3
标识
DOI:10.1615/jenvironpatholtoxicoloncol.2023049084
摘要
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.
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