铁死亡在宫颈癌治疗中的作用机制及研究进展

doi:10.3760/cma.j.cn371439-20250901-00135

国际肿瘤学杂志 ›› 2025, Vol. 52 ›› Issue (12): 791-794.doi: 10.3760/cma.j.cn371439-20250901-00135

铁死亡在宫颈癌治疗中的作用机制及研究进展

侯晓萱, 唐文洁, 谢鹏()

山东省肿瘤防治研究院（山东省肿瘤医院）妇科肿瘤放疗病区，山东第一医科大学附属肿瘤医院，山东第一医科大学（山东省医学科学院），济南 250117

收稿日期:2025-09-01 修回日期:2025-10-14 出版日期:2025-12-08 发布日期:2025-12-31
通讯作者: 谢鹏 E-mail:xiepeng100@126.com
基金资助:
中国博士后科学基金(2022M721446);山东省自然科学基金(ZR2022MH288);山东省博士后创新项目(SDCX-ZG-202303064);济南市临床医学科技创新计划(202430023);北京科创医学发展基金(KC2023-JX-0288-RM65);吴阶平医学基金会临床科研专项(320.6750.2023-17-26);新锐肿瘤支持治疗基金(cphcf-2023-10);山东第一医科大学教育教学改革研究项目(XM2022163);山东第一医科大学附属肿瘤医院学科集群创新工程(2024FC011)

Mechanism and research progress of ferroptosis in cervical cancer treatment

Hou Xiaoxuan, Tang Wenjie, Xie Peng()

Department of Gynecologic Radiation Oncology，Shandong Cancer Hospital and Institute， Cancer Hospital of Shandong First Medical University， Shandong First Medical University and Shandong Academy of Medical Sciences，Jinan 250117，China

Received:2025-09-01 Revised:2025-10-14 Online:2025-12-08 Published:2025-12-31
Contact: Xie Peng E-mail:xiepeng100@126.com
Supported by:
China Postdoctoral Science Foundation(2022M721446);Natural Science Foundation of Shandong Province(ZR2022MH288);Shandong Postdoctoral Science Foundation(SDCX-ZG-202303064);Jinan Clinical Medicine Science and Technology Innovation Plan(202430023);Beijing Science and Technology Innovation Medical Development Foundation(KC2023-JX-0288-RM65);Wu Jieping Medical Foundation Clinical Research Special Project(320.6750.2023-17-26);Xinrui Cancer Supportive Treatment Foundation(cphcf-2023-10);Education and Teaching Reform Research Project of Shandong First Medical University(XM2022163);Collaborative Academic Innovation Project of Cancer Hospital of Shandong First Medical University(2024FC011)

摘要/Abstract

摘要：

宫颈癌的病理进展与铁代谢调控及氧化应激密切相关。铁死亡作为一种铁依赖性的程序性细胞死亡形式，与宫颈癌的发生发展显著相关。与凋亡、坏死等传统细胞死亡途径不同，铁死亡显示出明显的特异性，其主要标志包括脂质过氧化、铁积累以及抗氧化系统功能抑制。铁死亡在抗肿瘤方面效果颇佳，展现出良好的应用前景，在与放疗、化疗等传统方法联用时表现出协同增效的潜力。探讨铁死亡与宫颈癌关联的分子基础及研究前沿动态，深入揭示其作用机制，可为宫颈癌治疗策略的创新提供理论依据与实践路径。

关键词: 宫颈肿瘤, 铁死亡, 脂质过氧化作用, 肿瘤治疗方案

Abstract:

The pathological progression of cervical cancer is closely related to iron metabolism regulation and oxidative stress. Ferroptosis， as a form of iron-dependent programmed cell death， has a significant association with the occurrence and development of cervical cancer. Unlike traditional cell death pathways such as apoptosis and necrosis， ferroptosis shows distinct specificity. Its main characteristics include lipid peroxidation， iron accumulation， and inhibition of the antioxidant system. Ferroptosis has shown excellent efficacy in antitumor treatment and has promising application prospects. When combined with traditional methods such as radiotherapy and chemotherapy， it demonstrates potential for synergistic enhancement. Further exploration of the molecular basis and research advances in the relationship between ferroptosis and cervical cancer， and delving into its underlying mechanism of action， can provide a theoretical foundation and practical guidance for innovative treatment strategies for cervical cancer.

Key words: Uterine cervical neoplasms, Ferroptosis, Lipid peroxidation, Antineoplastic protocols

侯晓萱, 唐文洁, 谢鹏. 铁死亡在宫颈癌治疗中的作用机制及研究进展[J]. 国际肿瘤学杂志, 2025, 52(12): 791-794.

Hou Xiaoxuan, Tang Wenjie, Xie Peng. Mechanism and research progress of ferroptosis in cervical cancer treatment[J]. Journal of International Oncology, 2025, 52(12): 791-794.

参考文献 37

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.
[2]	Perkins RB, Wentzensen N, Guido RS, et al. Cervical cancer scree-ning: a review[J]. JAMA, 2023, 330(6): 547-558. DOI: 10.1001/jama.2023.13174.
[3]	Mayadev JS, Ke G, Mahantshetty U, et al. Global challenges of radiotherapy for the treatment of locally advanced cervical cancer[J]. Int J Gynecol Cancer, 2022, 32(3): 436-445. DOI: 10.1136/ijgc-2021-003001. pmid: 35256434
[4]	Duska LR, Podwika SE, Randall LM. Top advances of the year: cervical cancer[J]. Cancer, 2024, 130(15): 2571-2576. DOI: 10.1002/cncr.35334.
[5]	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042. pmid: 22632970
[6]	Dixon SJ, Olzmann JA. The cell biology of ferroptosis[J]. Nat Rev Mol Cell Biol, 2024, 25(6): 424-442. DOI: 10.1038/s41580-024-00703-5.
[7]	Chen X, Li J, Kang R, et al. Ferroptosis: machinery and regulation[J]. Autophagy, 2021, 17(9): 2054-2081. DOI: 10.1080/15548627.2020.1810918.
[8]	Lei G, Zhuang L, Gan BY. The roles of ferroptosis in cancer: tumor suppression, tumor microenvironment, and therapeutic interventions[J]. Cancer Cell, 2024, 42(4): 513-534. DOI: 10.1016/j.ccell.2024.03.011. pmid: 38593779
[9]	Pope LE, Dixon SJ. Regulation of ferroptosis by lipid metabolism[J]. Trends Cell Biol, 2023, 33(12): 1077-1087. DOI: 10.1016/j.tcb.2023.05.003. pmid: 37407304
[10]	Zhang C, Liu X, Jin S, et al. Ferroptosis in cancer therapy: a novel approach to reversing drug resistance[J]. Mol Cancer, 2022, 21(1): 47. DOI: 10.1186/s12943-022-01530-y. pmid: 35151318
[11]	Xu LX, Hao LJ, Ma JQ, et al. SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase[J]. Mol Cell Biochem, 2020, 464(1/2): 11-20. DOI: 10.1007/s11010-019-03644-2.
[12]	Cruz-Gregorio A, Aranda-Rivera AK, Ortega-Lozano AJ, et al. Lipid metabolism and oxidative stress in HPV-related cancers[J]. Free Radic Biol Med, 2021, 172: 226-236. DOI: 10.1016/j.freeradbiomed.2021.06.009.
[13]	Wang T, Gong M, Cao Y, et al. Persistent ferroptosis promotes cervical squamous intraepithelial lesion development and oncogenesis by regulating KRAS expression in patients with high risk-HPV infection[J]. Cell Death Discov, 2022, 8(1): 201. DOI: 10.1038/s41420-022-01013-5. pmid: 35422066
[14]	Li J, Cao F, Yin HL, et al. Ferroptosis: past, present and future[J]. Cell Death Dis, 2020, 11(2): 88. DOI: 10.1038/s41419-020-2298-2. pmid: 32015325
[15]	Lee S, Hwang N, Seok BG, et al. Autophagy mediates an amplification loop during ferroptosis[J]. Cell Death Dis, 2023, 14(7): 464. DOI: 10.1038/s41419-023-05978-8. pmid: 37491375
[16]	Zhou Q, Meng Y, Li D, et al. Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies[J]. Signal Transduct Target Ther, 2024, 9(1): 55. DOI: 10.1038/s41392-024-01769-5.
[17]	Chen S, Shen L, Luo S, et al. Association between serum iron levels and the risk of cervical cancer in Chinese: a meta-analysis[J]. J Int Med Res, 2020, 48(3): 300060519882804. DOI: 10.1177/0300060519882804.
[18]	Braun JA, Herrmann AL, Blase JI, et al. Effects of the antifungal agent ciclopirox in HPV-positive cancer cells: repression of viral E6/E7 oncogene expression and induction of senescence and apoptosis[J]. Int J Cancer, 2020, 146(2): 461-474. DOI: 10.1002/ijc.32709. pmid: 31603527
[19]	Huang N, Wei Y, Cheng Y, et al. Iron metabolism protein transferrin receptor 1 involves in cervical cancer progression by affecting gene expression and alternative splicing in HeLa cells[J]. Genes Genomics, 2022, 44(6): 637-650. DOI: 10.1007/s13258-021-01205-w.
[20]	Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015, 520(7545): 57-62. DOI: 10.1038/nature14344.
[21]	Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer[J]. Nat Rev Cancer, 2022, 22(7): 381-396. DOI: 10.1038/s41568-022-00459-0. pmid: 35338310
[22]	Chen Z, Wang W, Abdul Razak SR, et al. Ferroptosis as a potential target for cancer therapy[J]. Cell Death Dis, 2023, 14(7): 460. DOI: 10.1038/s41419-023-05930-w. pmid: 37488128
[23]	Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease[J]. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282. DOI: 10.1038/s41580-020-00324-8.
[24]	Wu P, Li C, Ye DM, et al. Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis[J]. Aging (Albany NY), 2021, 13(3): 4663-4673. DOI: 10.18632/aging.202518.
[25]	Liu Y, Li L, Yang Z, et al. Circular RNA circACAP2 suppresses ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4[J]. J Oncol, 2022, 2022: 5228874. DOI: 10.1155/2022/5228874.
[26]	Chen X, Kang R, Kroemer G, et al. Broadening horizons: the role of ferroptosis in cancer[J]. Nat Rev Clin Oncol, 2021, 18(5): 280-296. DOI: 10.1038/s41571-020-00462-0. pmid: 33514910
[27]	Zheng C, Wang C, Sun D, et al. Structure-activity relationship study of RSL3-based GPX4 degraders and its potential noncovalent optimization[J]. Eur J Med Chem, 2023, 255: 115393. DOI: 10. 1016/j.ejmech.2023.115393.
[28]	Wei X, Huang Q, Huang J, et al. Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway[J]. Int J Immunopathol Pharmacol, 2023, 37: 3946320231219348. DOI: 10.1177/03946320231219348.
[29]	Du Y, Guo Z. Recent progress in ferroptosis: inducers and inhibitors[J]. Cell Death Discov, 2022, 8(1): 501. DOI: 10.1038/s41420-022-01297-7. pmid: 36581640
[30]	Zhang Z, Hu Q, Ye S, et al. Inhibition of the PIN1-NRF2/GPX4 axis imparts sensitivity to cisplatin in cervical cancer cells[J]. Acta Biochim Biophys Sin (Shanghai), 2022, 54(9): 1325-1335. DOI: 10.3724/abbs.2022109.
[31]	Wang X, Du Q, Mai Q, et al. Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer[J]. Transl Oncol, 2025, 56: 102396. DOI: 10.1016/j.tranon.2025.102396.
[32]	Chang X, Miao J. Ferroptosis: mechanism and potential applications in cervical cancer[J]. Front Mol Biosci, 2023, 10: 1164398. DOI: 10.3389/fmolb.2023.1164398.
[33]	Ding Q, Zhuang Y, Yang HY, et al. USP31 confers radio-resistance in cervical cancer cells via ferroptosis pathway by deubiquitinating and stabilizing GPX4[J]. Biochem Biophys Res Commun, 2025, 770: 151990. DOI: 10.1016/j.bbrc.2025.151990.
[34]	Lei G, Zhang Y, Koppula P, et al. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression[J]. Cell Res, 2020, 30(2): 146-162. DOI: 10.1038/s41422-019-0263-3. pmid: 31949285
[35]	Fan F, Liu P, Bao R, et al. A dual PI3K/HDAC inhibitor induces immunogenic ferroptosis to potentiate cancer immune checkpoint therapy[J]. Cancer Res, 2021, 81(24): 6233-6245. DOI: 10.1158/0008-5472.CAN-21-1547. pmid: 34711611
[36]	Zeng F, Nijiati S, Tang L, et al. Ferroptosis detection: from approaches to applications[J]. Angew Chem Int Ed Engl, 2023, 62(35): e202300379. DOI: 10.1002/ange.202300379.
[37]	Wang D, Wang Z, Ren X, et al. A multifunctional bimetallic nanoplatform for enhancing radiotherapy via oxidative damage and ferroptosis of cervical cancer[J]. Sep Purif Technol, 2024, 338: 126567. DOI: 10.1016/j.seppur.2024.126567.

铁死亡在宫颈癌治疗中的作用机制及研究进展

Mechanism and research progress of ferroptosis in cervical cancer treatment

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