铁死亡在肾细胞癌发生发展和治疗中的作用及机制研究进展

铁死亡是以细胞内铁超载和活性氧聚集引起脂质过氧化为特征的新型细胞死亡方式,主要是有谷胱甘肽过氧化物酶（glutathione peroxidase 4,GPX4）缺乏、铁代谢异常、脂质过氧化等原因导致的细胞死亡。肾细胞癌是泌尿系统常见的恶性肿瘤之一,早期肾细胞癌有治愈的可能,但晚期和转移性肾细胞癌的治疗依旧是一大难点。近年来铁死亡在肿瘤中治疗作用越来越被关注,铁死亡可以通过调节细胞内铁离子水平和脂质过氧化水平,从而调控细胞死亡。因此,铁死亡有望成为有效治疗肾细胞癌的策略。本文主要介绍铁死亡的调控机制及其在肾细胞癌中的作用机制,旨在为改进治疗和开创新疗法提供新思路。     

铁死亡在肿瘤转移中作用的研究进展

铁死亡是新发现的以过氧化脂质和活性氧堆积、游离铁增加为主要特征的程序性死亡方式, 涉及谷胱甘肽代谢、铁代谢、脂质代谢和氧化应激生物学过程。肿瘤转移是肿瘤恶性程度的重要特征, 也是癌症患者复发和死亡的主要原因之一, 近年来大量研究表明铁死亡与肿瘤发生、发展密切相关, 并提示铁死亡诱导剂有望成为防治肿瘤转移的新策略。文章就铁死亡相关调控机制及其在肿瘤转移侵袭、循环、定植3个阶段中的作用进行综述。     

谷胱甘肽过氧化物酶GPX4在铁死亡中的作用与机制研究进展

谷胱甘肽过氧化物酶4(GPX4)是一种能够特异性催化谷胱甘肽将脂质过氧化物转化为类脂醇的硒蛋白,它在调节细胞铁死亡方面发挥着重要的作用。本文将对GPX4的蛋白结构、分子作用机制及其表达调控进行介绍,对其在铁死亡中的功能以及在癌症等疾病中的应用进行系统综述,对未来存在的问题进行了分析与展望。     

铁死亡在消化系统肿瘤中的研究进展

铁死亡是一种新近发现的程序性细胞死亡形式,其过程主要表现为铁依赖的膜结构脂质过氧化损伤,进而导致细胞的完整性破坏并崩解死亡.铁死亡参与了包括肿瘤、缺血再灌注损伤、急性肾损伤和神经系统疾病等在内的多种疾病过程.铁死亡在肿瘤的发生发展中发挥重要作用,尤其对消化系统肿瘤存在较大的潜在临床转化研究意义.本文对铁死亡的发生机制以...     

铁死亡纳米探针在肿瘤治疗中应用的研究进展

铁死亡是新发现的一种异于凋亡形式的细胞死亡形式，是一种新型的铁依赖型程序性细胞死亡的过程。铁死亡与脂质过氧化和铁离子代谢密切相关。近年来已经开发出许多纳米探针结合铁死亡疗法来进行肿瘤治疗。其构建的主要思路是通过增强肿瘤细胞内芬顿反应与消耗谷胱甘肽（glutathione，GSH）或者使谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）失活导致氧化损伤两种途径。本文将对使用铁死亡纳米探针在肿瘤治疗中的最新研究进展及应用进行综述。     

铁死亡调控通路及其在肿瘤放化疗和免疫治疗抵抗中的研究进展

铁死亡是一种由Fe2+触发、脂质过氧化物蓄积致损伤的细胞死亡方式。铁死亡的调控机制复杂,主要涉及铁稳态调节通路、脂质代谢通路及胱氨酸/谷氨酸转运通路等。目前研究发现铁死亡在肿瘤发生、发展及治疗中均具有重要作用。因此,更好地分析铁死亡及其在肿瘤耐药、免疫逃逸中的调控机制,将有助于发现新的治疗策略,以最终改善肿瘤患者预后。本综述通过对肿瘤细胞铁死亡调节通路进行概述,并分析铁死亡与肿瘤放化疗抵抗、免疫治疗的相互作用,希望为肿瘤综合治疗提供新的思路。     

铁死亡在肿瘤耐药中作用的研究进展

肿瘤耐药是一个多基因、多信号通路的复杂过程,越来越多的证据表明,活性氧（reactive oxygen species,ROS）失衡介导的氧化应激防御和ROS相关的铁死亡与肿瘤耐药密切相关。新近发现,肿瘤细胞可能通过负向调节铁死亡,显著增强其氧化应激防御能力,导致肿瘤耐药。铁死亡是一种铁依赖的、脂质过氧化物累积所触发驱动的一种调节性细胞死亡方式。由谷胱甘肽耗尽或谷胱甘肽过氧化物酶4（glutathione peroxidase 4,GPX4）的失活导致的致死性代谢失衡是铁死亡过程的特征。在耐药环境下,小分子化合物诱导的铁死亡具有强烈抑制肿瘤生长的作用,可增强化疗药物敏感性,提示铁死亡在肿瘤药物耐药治疗中的作用十分重要,但有关细节仍不清楚。概述肿瘤细胞对氧化应激耐受的机制,强调铁死亡在其中的作用,并讨论肿瘤耐药治疗的策略。     

γ-谷氨酰转移酶促进恶性肿瘤发生与发展的研究进展北大核心CSCD

γ-谷氨酰转移酶(gamma-glutamyltransferase,GGT)作为谷胱甘肽(glutathione,GSH)代谢过程中的关键酶之一,广泛分布于人体内各组织器官中,参与细胞氧化还原调控、解毒及铁死亡等过程。GGT在多种原发性和转移性肿瘤中表达水平异常升高,而且GGT高表达与肿瘤恶性程度高及预后不良明显相关。近年来有研究认为,血清及外泌体内高GGT活性会增加多种恶性肿瘤的发病风险,并且与患者的不良预后相关,提示GGT可能是潜在的肿瘤治疗靶标和肿瘤诊断及预后判断的标志物。本文就组织及外周血中GGT表达与恶性肿瘤发生与发展的关系,以及其临床意义和调控机制的研究进展进行综述。     

自噬在细胞铁死亡发生中作用机制的研究进展

铁死亡（ferroptosis）是近年来新发现的一种非凋亡性细胞程序性死亡方式,以铁依赖性和脂质活性氧(lipid reactive oxygen species,L-ROS)累积为特征。自噬是真核生物中的高度保守的生物代谢过程,广泛参与机体生物调节。研究发现细胞铁死亡与自噬在肿瘤发生发展中关系密切,自噬调控基因及相关信号通路与铁死亡过程发生交互调节,影响细胞死亡进程。本文将概述铁死亡与自噬的发生及调节机制,综述自噬在铁死亡发生过程中的作用,展望利用自噬与铁死亡的相互作用对肿瘤治疗的意义。     

放射性肺损伤与铁死亡相关性研究进展

放射性肺损伤(RILI)是肺癌等胸部肿瘤放疗后的常见并发症,而铁死亡是一种由铁依赖的、膜脂质过氧化引起的调节性细胞死亡。本文主要从活性氧簇诱导的氧化损伤、核因子E2相关因子2调控的抗氧化网络和铁离子稳态以及转化生长因子β1参与的炎性反应方面来探索RILI和铁死亡之间关系,以期通过调控铁死亡以减轻或抑制RILI发生,从而...     

铁死亡在泌尿系肿瘤治疗中的研究进展

铁死亡是一种不同于凋亡、自噬、坏死的程序性细胞死亡方式,已有研究表明铁死亡与退行性疾病、缺血-再灌注损伤、肾损伤、肿瘤等疾病相关。泌尿系肿瘤发病率逐年递增,而治疗效果不佳。因此,探究铁死亡在泌尿系肿瘤中的潜在治疗效果可能作为一种新的治疗方式。本文主要总结了铁死亡发展历程、核心机制以及在泌尿系肿瘤中的研究现状。将铁死亡和现有的肿瘤治疗方式结合有助于增加其抗肿瘤治疗和克服肿瘤的耐药性。但铁死亡在泌尿系肿瘤中的研究相对较少,深入探究其作用机制有助于将其应用于临床抗肿瘤治疗。     

Novel perspective in pancreatic cancer therapy: Targeting ferroptosis pathway

Pancreatic cancer is a highly lethal malignancy with low resection and survival rates and is not sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of nonapoptotic regulated cell death characterized by the accumulation of lipid peroxides and reactive oxygen species involved in iron metabolism. Ferroptosis has a significant role in the occurrence and development of various tumors. Previous studies have shown that regulating ferroptosis-induced cell death inhibited tumor growth in pancreatic cancer and was synergistic with other antitumor drugs to improve treatment sensitivity. Herein, we discuss the mechanism, inducers, and developments of ferroptosis in pancreatic cancer to provide new strategies for the treatment of the malignancy.     

铁死亡的代谢关联机制及其在肿瘤免疫治疗中的作用研究进展

铁死亡作为一种新的调节性细胞死亡方式,其特征是铁依赖性的脂质活性氧(reactive oxygen species,ROS)的过量蓄积.该过程与多种生物学途径相关,包括氨基酸代谢、铁代谢及脂质代谢等.目前,已知铁死亡与恶性肿瘤的发生、发展和治疗关系密切,且在肿瘤免疫调节中发挥双重作用,一方面促进肿瘤细胞铁死亡以介导抗肿...     

Targeting ferroptosis for cancer therapy: iron metabolism and anticancer immunity

Ferroptosis is a new form of programmed cell death characterized by iron-dependent accumulation of lipid peroxidation, which plays an important role in cancer biology. Ferroptosis is involved in many biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism. Iron is an essential trace element in a variety of normal cell processes, such as DNA synthesis and repair, cell respiration, metabolism and signal transduction, etc., and iron metabolism disorder has been considered as one of the metabolic markers of malignant cancer cells. In addition, iron is involved in the regulation of innate and adaptive immune responses, suggesting that targeted regulation of iron metabolism may contribute to anti-tumor immunity and cancer therapy. In this review, the regulatory mechanism of ferroptosis, the interaction between ferroptosis on tumor cell metabolism, and anti-tumor immunity were systematically reviewed. Immunotherapy combined with targeted regulation of iron and iron-dependent regulation of ferroptosis should be the focus of future ferroptosis research.     

基于铁死亡的纳米联合疗法在恶性肿瘤治疗中的研究进展

铁死亡作为一种有潜力的恶性肿瘤治疗策略,日益引起广泛关注。铁死亡是一种铁依赖的调节性细胞死亡方式,其典型特征为细胞内活性氧的蓄积和脂质过氧化。随着纳米技术和生物材料技术的快速发展,多功能纳米制剂介导的铁死亡联合疗法在肿瘤诊断与治疗上显示出巨大的临床应用前景。本文就纳米制剂诱导的铁死亡作用机制及基于铁死亡的联合抗肿瘤疗法的最新研究进展进行综述,并总结了铁死亡疗法在临床肿瘤治疗中的应用前景与挑战,以期为发展新型高效的抗肿瘤策略提供新思路。     

Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates

Gastrointestinal (GI) tumors, including liver, pancreatic, gastric, and colorectal cancers, have a high incidence rate and low survival rate due to the lack of effective therapeutic methods and frequent relapses. Surgery and postoperative chemoradiotherapy have largely reduced the fatality rates for most GI tumors, but these therapeutic approaches result in poor prognoses due to severe adverse reactions and the development of drug resistance. Recent studies have shown that ferroptosis plays an important role in the onset and progression of GI tumors. Ferroptosis is a new non-apoptotic form of cell death, which is iron-dependent, non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species (ROS). The activation of ferroptosis can lead to tumor cell death. Thus, regulating ferroptosis in tumor cells may become a new therapeutic approach for tumors, making it become a research hotspot. Current studies suggest that ferroptosis is mainly triggered by the accumulation of lipid ROS. Furthermore, several studies have indicated that ferroptosis may be a new approach for the treatment of GI tumors. Here, we review current research progress on the mechanism of ferroptosis, current inducers and inhibitors of ferroptosis, and the role of ferroptosis in GI tumors to propose new methods for the treatment of such tumors.     

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

Ferroptosis is an iron‐dependent, lipid peroxide‐driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple‐negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin‐loaded exosomes labeled with folate (FA) to form FA‐vectorized exosomes loaded with erastin (erastin@FA‐exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti–tumor effect in vitro of erastin@FA‐exo were determined. Erastin@FA‐exo could increase the uptake efficiency of erastin into MDA‐MB‐231 cells; compared with erastin@exo and free erastin, erastin@FA‐exo has a better inhibitory effect on the proliferation and migration of MDA‐MB‐231 cells. Furthermore, erastin@FA‐exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA‐exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome‐based erastin preparations provide an innovative and powerful delivery platform for anti–cancer therapy.