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用中药单体靶向胃癌中的铁死亡和免疫监视:上皮-间质转化和血管生成的双靶点策略

Targeting ferroptosis and immune surveillance in gastric cancer with traditional Chinese medicine monomers: a dual-targeted strategy for epithelial-mesenchymal transition and angiogenesis.

作者信息

Ma Yijia, Han Lichao, Ni Qianyue, Liang Hao, Chen Baojiang, Wang Zijian, Jia Yu, Xu Yimin, Liu Zheng

机构信息

Heilongjiang University of Chinese Medicine Harbin 150040, Heilongjiang, China.

The First Affiliated Hospital of Heilongjiang University of Chinese Medicine Harbin 150040, Heilongjiang, China.

出版信息

Am J Cancer Res. 2025 Aug 25;15(8):3617-3631. doi: 10.62347/KSKH3925. eCollection 2025.

DOI:10.62347/KSKH3925
PMID:40948538
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12432575/
Abstract

Gastric cancer (GC) is a highly prevalent and lethal malignancy worldwide. Tumor progression is driven by epithelial-mesenchymal transition (EMT) and aberrant angiogenesis, which collectively facilitate invasion, metastasis, and immune evasion. Ferroptosis, a form of programmed cell death induced by iron-dependent lipid peroxidation, has recently emerged as a promising mechanism to eliminate GC cells, overcome apoptosis resistance, and inhibit migration. Remodeling the tumor immune microenvironment to enhance immune surveillance represents another advanced therapeutic strategy. Natural compounds derived from traditional Chinese medicine (TCM), such as quercetin and curcumin, exert multi-targeted anti-tumor effects by modulating ferroptosis, EMT, angiogenesis, and the immune microenvironment. This review synthesizes evidence from both in vitro and in vivo studies supporting the role of TCM monomers in co-regulating ferroptosis and immune surveillance in GC. Furthermore, it proposes a dual-target approach against EMT and angiogenesis to advance the theoretical framework and promote the clinical application of TCM in precision oncology, thereby guiding the development of novel, low-toxicity, and high-efficacy anti-cancer agents.

摘要

胃癌(GC)是全球范围内一种高度普遍且致命的恶性肿瘤。肿瘤进展由上皮-间质转化(EMT)和异常血管生成驱动,它们共同促进侵袭、转移和免疫逃逸。铁死亡是一种由铁依赖性脂质过氧化诱导的程序性细胞死亡形式,最近已成为一种有前景的消除GC细胞、克服凋亡抗性和抑制迁移的机制。重塑肿瘤免疫微环境以增强免疫监视是另一种先进的治疗策略。源自中药(TCM)的天然化合物,如槲皮素和姜黄素,通过调节铁死亡、EMT、血管生成和免疫微环境发挥多靶点抗肿瘤作用。本综述综合了体外和体内研究的证据,支持中药单体在共同调节GC中铁死亡和免疫监视方面的作用。此外,它提出了一种针对EMT和血管生成的双靶点方法,以推进理论框架并促进中药在精准肿瘤学中的临床应用,从而指导新型、低毒和高效抗癌药物的开发。

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Targeting ferroptosis and immune surveillance in gastric cancer with traditional Chinese medicine monomers: a dual-targeted strategy for epithelial-mesenchymal transition and angiogenesis.用中药单体靶向胃癌中的铁死亡和免疫监视:上皮-间质转化和血管生成的双靶点策略
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本文引用的文献

1
Resveratrol targets mitochondrial USP36-SOD2 to induce autophagy-ferroptosis and inhibit gastric cancer progression.白藜芦醇靶向线粒体USP36-SOD2以诱导自噬-铁死亡并抑制胃癌进展。
Gastric Cancer. 2025 Jul 12. doi: 10.1007/s10120-025-01645-3.
2
Ginsenosides and gastrointestinal cancers: A novel therapeutic strategy in cancer therapy.人参皂苷与胃肠道癌症:癌症治疗中的一种新型治疗策略。
Pathol Res Pract. 2025 Aug;272:156078. doi: 10.1016/j.prp.2025.156078. Epub 2025 Jul 8.
3
Ferroptosis in immune cells: Implications for tumor immunity and cancer therapy.免疫细胞中的铁死亡:对肿瘤免疫和癌症治疗的影响。
Cytokine Growth Factor Rev. 2025 Aug;84:59-73. doi: 10.1016/j.cytogfr.2025.06.007. Epub 2025 Jun 24.
4
Targeting Ferroptosis in Tumors: Novel Marine-Derived Compounds as Regulators of Lipid Peroxidation and GPX4 Signaling.靶向肿瘤中的铁死亡:新型海洋来源化合物作为脂质过氧化和谷胱甘肽过氧化物酶4信号通路的调节剂
Mar Drugs. 2025 Jun 19;23(6):258. doi: 10.3390/md23060258.
5
Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.靶向铁死亡用于癌症治疗的食物衍生化合物:从作用到机制
Front Oncol. 2025 Jun 9;15:1568391. doi: 10.3389/fonc.2025.1568391. eCollection 2025.
6
Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.上皮-间质转化(EMT)与癌症转移:2025年方法与实验模型的现状
Mol Cancer. 2025 Jun 7;24(1):167. doi: 10.1186/s12943-025-02338-2.
7
A review on anti-cancer properties of quercetin in gastric cancer.槲皮素对胃癌抗癌特性的综述。
Front Pharmacol. 2025 May 19;16:1563229. doi: 10.3389/fphar.2025.1563229. eCollection 2025.
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Quercetin Inhibits Gastric Cancer Progression via FAM198B/MAPK Pathway Modulation.槲皮素通过FAM198B/丝裂原活化蛋白激酶(MAPK)信号通路调控抑制胃癌进展。
Pharmgenomics Pers Med. 2025 May 15;18:115-141. doi: 10.2147/PGPM.S511324. eCollection 2025.
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Recent advancement in the anticancer efficacy of the natural flavonoid scutellarin: a comprehensive review.天然黄酮类化合物灯盏花素抗癌疗效的最新进展:综述
Front Pharmacol. 2025 Mar 27;16:1579609. doi: 10.3389/fphar.2025.1579609. eCollection 2025.
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Cell Death Discov. 2025 Apr 1;11(1):128. doi: 10.1038/s41420-025-02415-x.