铁死亡抑制蛋白1（FSP1）-辅酶Q10（CoQ10）和二氢乳清酸脱氢酶（DHODH）双通路在肝细胞癌铁死亡中的作用及其临床意义

杨晶涵; 王中峰; 王越晖

doi:10.12449/JCH260331

铁死亡抑制蛋白1（FSP1）-辅酶Q10（CoQ10）和二氢乳清酸脱氢酶（DHODH）双通路在肝细胞癌铁死亡中的作用及其临床意义

DOI: 10.12449/JCH260331

1.
吉林大学第一医院老年病科，长春 130021
2.
吉林大学第一医院肝胆胰内科，长春 130021

基金项目:

吉林省医疗卫生人才专项项目 (JLSRCZX2025-018)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：杨晶涵负责资料分析，撰写论文；王中峰参与查阅文献，修改论文；王越晖负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
王越晖， yuehuiwang300@jlu.edu.cn （ORCID： 0009-0003-3103-1504）

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出版历程
- 收稿日期: 2025-09-23
- 录用日期: 2025-10-14
- 出版日期: 2026-03-25

Dual ferroptosis suppressor protein 1-coenzyme Q10 and dihydroorotate dehydrogenase pathways in ferroptosis of hepatocellular carcinoma： Mechanisms and its clinical significance

1.
Department of Geriatrics，The First Hospital of Jilin University，Changchun 130021，China
2.
Department of Hepatopancreatobiliary Medicine，The First Hospital of Jilin University，Changchun 130021，China

Research funding:

Jilin Provincial Special Program for Healthcare Talents (JLSRCZX2025-018)

More Information

Corresponding author: WANG Yuehui， yuehuiwang300@jlu.edu.cn （ORCID： 0009-0003-3103-1504）

摘要

摘要: 肝细胞癌（HCC）是全球常见且致死率高的恶性肿瘤，患者总体生存获益有限、耐药问题突出，亟需新的增敏策略和分层体系。铁死亡是一种铁依赖的脂质过氧化细胞死亡形式，与肿瘤治疗反应密切相关。除经典的谷胱甘肽过氧化物酶4（GPX4）/谷胱甘肽（GSH）通路外，铁死亡抑制蛋白1（FSP1）-辅酶Q10（CoQ10）和二氢乳清酸脱氢酶（DHODH）是两条新的抗铁死亡通路，分别在质膜和线粒体发挥作用，与GPX4协同决定细胞对铁死亡的敏感性。本文系统综述了FSP1-CoQ10和DHODH通路在HCC中的作用机制与研究进展，并提出相关治疗策略以及展望其临床转化应用前景。
- 癌，肝细胞 /
- 铁死亡 /
- 信号传导 /
- 病理过程 /
- 治疗学
Abstract: Hepatocellular carcinoma （HCC） is a common malignant tumor with a high fatality rate worldwide， with limited overall survival benefits and pronounced drug resistance issues， highlighting the urgent need for novel sensitization strategies and patient stratification systems. Ferroptosis， as an iron-dependent form of lipid peroxidation-driven cell death， is closely associated with tumor treatment responses. In addition to the classic glutathione peroxidase 4 （GPX4）/glutathione （GSH） pathway， the ferroptosis suppressor protein 1 （FSP1）-coenzyme Q10 （CoQ10） pathways and the dihydroorotate dehydrogenase （DHODH） pathway are two newly identified anti-ferroptosis pathways that function at the plasma membrane and mitochondria， respectively， and determine cellular sensitivity to ferroptosis in synergy with GPX4. This article systematically reviews the mechanism of action of the FSP1-CoQ10 and DHODH pathways in HCC and related research advances， proposes related therapeutic strategies， and look forward to its clinical translation and application prospects.
- Carcinoma， Hepatocellular /
- Ferroptosis /
- Signal Transduction /
- Pathologic Processes /
- Therapeutics

HTML全文

注： DHODH，二氢乳清酸脱氢酶；DHO，二氢乳清酸；Orotate，乳清酸根；CoQ/CoQH₂，辅酶Q/泛醌醇；System Xc⁻，胱氨酸/谷氨酸反向转运系统；GSH，谷胱甘肽；LOOH，脂质过氧化物；GPX4，谷胱甘肽过氧化物酶4；TRIM54/21，含三联结构域蛋白54/21；lncFAL，铁死亡相关长链非编码RNA；Keap1/Nrf2，Kelch样ECH相关蛋白1/核因子E2相关因子2；MVA，甲羟戊酸；FSP1，铁死亡抑制蛋白1；AIFM2，凋亡诱导因子线粒体相关蛋白2；NAD（P）H，还原型烟酰胺腺嘌呤二核苷酸；FGFR4，成纤维生长因子受体4；MHC-Ⅰ，主要组织相容性复合体Ⅰ类分子；ACSL4/LPCAT3，长链脂酰辅酶A合成酶4/溶血磷脂酰胆碱酰基转移酶3；PUFA-PL，多不饱和脂肪酸磷脂；MDA/4-HNE/C11-BODIPY，丙二醛/4-羟基壬烯醛/C11-BODIPY探针。

图 1 FSP1-CoQ10与DHODH双通路在肝细胞癌铁死亡中的作用机制与转化策略

Figure 1. Dual-pathway mechanism and translational strategy of FSP1-CoQ10 and DHODH in ferroptosis of HCC

下载: 全尺寸图片幻灯片

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