铁死亡与乳腺癌患者化疗耐药的关系研究进展

doi:10.3760/cma.j.issn.1007-1245.2024.03.001

摘要/Abstract

摘要：

乳腺癌作为女性常见的恶性肿瘤，已跃居女性恶性肿瘤之首，对女性健康产生严重影响。目前，虽然乳腺癌的治疗方法多种多样，但是由于患者存在恶性程度高、化疗耐药等问题，使得其临床治疗效果不佳，严重影响患者预后和生存。铁死亡作为一种新型的细胞死亡形式，以细胞内铁过表达和脂质活性氧累积为特征。研究发现，铁死亡与乳腺癌的发生发展及演进有关，并且诱导铁死亡可以抑制乳腺癌细胞的增殖及远处转移，增强其化疗药物的疗效，进而逆转乳腺癌化疗耐药。因此，诱导铁死亡可成为乳腺癌患者临床治疗的新策略。本文对乳腺癌化疗耐药、铁死亡作用机制及其在乳腺癌患者治疗中的研究进展进行综述。

关键词:

铁死亡, 乳腺癌, 化疗, 化疗耐药, 进展

Abstract:

As a common malignant tumor in women, breast cancer has risen to the top of female malignant tumors, and has serious impact on women's health. At present, although there are various treatment methods for breast cancer, due to the high degree of malignancy and chemotherapy resistance of patients, the clinical treatment effect is not good, which seriously affects the patients' prognosis and survival. Iron death is a novel form of cell death characterized by intracellular iron overexpression and lipid reactive oxygen species accumulation. Studies have found that iron death is related to the occurrence, development, and evolution of breast cancer, so inducing iron death can inhibit the proliferation and distant metastasis of breast cancer cells, enhance the efficacy of chemotherapy drugs, and reverse the chemotherapy resistance of breast cancer. Therefore, inducing iron death may become a new strategy for clinical treatment of patients with breast cancer. In this paper, the mechanism of chemotherapy resistance and iron death in breast cancer and the research progress in the treatment of patients with breast cancer are reviewed.

Key words:

Iron death, Breast cancer, Chemotherapy, Chemotherapy resistance, Progress

于潇杰程立浩张浩张浩杰杨振林.

铁死亡与乳腺癌患者化疗耐药的关系研究进展 [J]. 国际医药卫生导报, 2024, 30(3): 353-356.

Yu Xiaojie, Cheng Lihao, Zhang Hao, Zhang Haojie, Yang Zhenlin.

Research progress on relationship between iron death and chemotherapy resistance in patients with breast cancer [J]. International Medicine and Health Guidance News, 2024, 30(3): 353-356.

参考文献

[1] Onkar SS, Carleton NM, Lucas PC, et al. The great immune escape: understanding the divergent immune response in breast cancer subtypes [J]. Cancer Discov, 2023, 13(1): 23-40. DOI: 10.1158/2159-8290.CD-22-0475.
[2] Zhang L, Chen W, Liu S, et al. Targeting breast cancer stem cells [J]. Int J Biol Sci, 2023, 19(2): 552-570. DOI: 10.7150/ijbs.76187.
[3] 李卫星. 阿帕替尼治疗复发性三阴乳腺癌的临床疗效分析[J]. 国际医药卫生导报, 2020, 26(21): 3287-3290. DOI: 10.3760/cma.j.issn.1007-1245.2020.21.028.
[4] Latunde-Dada GO. Ferroptosis: role of lipid peroxidation, iron and ferritinophagy [J]. Biochim Biophys Acta Gen Subj, 2017, 1861(8): 1893-1900. DOI: 10.1016/j.bbagen.2017.05.019.
[5] Nedeljković M, Damjanović A. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge [J]. Cells, 2019, 8(9): 957. DOI: 10.3390/cells8090957.
[6] Ford RC, Beis K. Learning the ABCs one at a time: structure and mechanism of ABC transporters [J]. Biochem Soc Trans, 2019, 47(1): 23-36. DOI: 10.1042/BST20180147.
[7] Rouhrazi H, Turgan N, Oktem G. Zoledronic acid overcomes chemoresistance by sensitizing cancer stem cells to apoptosis [J]. Biotech Histochem, 2018, 93(2): 77-88. DOI: 10.1080/10520295.2017.1387286.
[8] Stockwell BR. Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications [J]. Cell, 2022, 185(14): 2401-2421. DOI: 10.1016/j.cell.2022.06.003.
[9] Fang X, Ardehali H, Min J, et al. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease [J]. Nat Rev Cardiol, 2023, 20(1): 7-23. DOI: 10.1038/s41569-022-00735-4.
[10] Shi Z, Zhang L, Zheng J, et al. Ferroptosis: biochemistry and biology in cancers[J]. Front Oncol, 2021, 11: 579286. DOI:10.3389/fonc.2021.579286.
[11] Wang S, Luo J, Zhang Z, et al. Iron and magnetic: new research direction of the ferroptosis-based cancer therapy [J]. Am J Cancer Res, 2018, 8(10): 1933-1946.
[12] 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.
[13] Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 49. DOI:10.1038/s41392-020-00428-9.
[14] Lu B, Chen XB, Ying MD, et al. The role of ferroptosis in cancer development and treatment response [J]. Front Pharmacol, 2017, 8: 992. DOI: 10.3389/fphar.2017.00992.
[15] Xu T, Ding W, Ji X, et al. Molecular mechanisms of ferroptosis and its role in cancer therapy [J]. J Cell Mol Med. 2019, 23(8): 4900-4912. DOI:10.1111/jcmm.14511
[16] Yang F, Xiao Y, Ding JH, et al. Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy [J]. Cell Metab, 2023, 35(1): 84-100. DOI: 10.1016/j.cmet.2022.09.021.
[17] Yu H, Yang C, Jian L, et al. Sulfasalazine‑induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor[J]. Oncol Rep, 2019, 42(2): 826-838. DOI: 10.3892/or.2019.7189.
[18] Li S, He Y, Chen K, et al. RSL3 drives ferroptosis through NF-kappaB pathway activation and GPX4 depletion in glioblastoma [J]. Oxid Med Cell Longev, 2021: 2915019. DOI: 10.1155/2021/2915019.
[19] Bai X, Ni J, Beretov J, et al. Activation of the eIF2alpha/ATF4 axis drives triple-negative breast cancer radioresistance by promoting glutathione biosynthesis [J]. Redox Biol, 2021, 43: 101993. DOI: 10.1016/j.redox.2021.101993.
[20] Chen MS, Wang SF, Hsu CY, et al. CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2alpha-ATF4 pathway [J]. Oncotarget, 2017, 8(70): 114588-114602. DOI: 10.18632/oncotarget.23055.
[21] Shi Z, Naowarojna N, Pan Z, et al. Author correction: multifaceted mechanisms mediating cystine starvation-induced ferroptosis [J]. Nat Commun, 2023, 14(1): 980. DOI: 10.1038/s41467-023-36659-x.
[22] Zhu J, Dai P, Liu F, et al. Upconverting nanocarriers enable triggered microtubule inhibition and concurrent ferroptosis induction for selective treatment of triple-negative breast cancer [J]. Nano Lett, 2020, 20(9): 6235-6245. DOI: 10.1021/acs.nanolett.0c00502.
[23] Antoniak MA, Pazik R, Bazylinska U, et al. Multimodal polymer encapsulated CdSe/Fe(3)O(4) nanoplatform with improved biocompatibility for two-photon and temperature stimulated bioapplications [J]. Mater Sci Eng C Mater Biol Appl, 2021, 127: 112224. DOI: 10.1016/j.msec.2021.112224.
[24] Ma S, Dielschneider RF, Henson ES, et al. Ferroptosis and autophagy induced cell death occur independently after siramesine and lapatinib treatment in breast cancer cells[J]. PLoS One. 2017, 12(8): e182921. DOI: 10.1371/journal.pone.0182921.
[25] Xu X, Chen Y, Zhang Y, et al. Highly stable and biocompatible hyaluronic acid-rehabilitated nanoscale MOF-Fe2+ induced ferroptosis in breast cancer cells [J]. J Mater Chem B, 2020. DOI: 10.1039/d0tb01616k.
[26] Du J, Wang L, Huang X, et al. Shuganning injection, a traditional Chinese patent medicine, induces ferroptosis and suppresses tumor growth in triple-negative breast cancer cells [J]. Phytomedicine, 2021, 85: 153551. DOI: 10.1016/j.phymed.2021.153551.
[27] Yang Y, Liu T, Hu C, et al. Ferroptosis inducer erastin downregulates androgen receptor and its splice variants in castration-resistant prostate cancer [J]. Oncol Rep, 2021, 45(4): 25. DOI: 10.3892/or.2021.7976.
[28] Song X, Wang X, Liu Z, et al. Role of GPX4-mediated ferroptosis in the sensitivity of triple negative breast cancer cells to gefitinib [J]. Front Oncol, 2020, 10: 597434. DOI: 10.3389/fonc.2020.597434.
[29] Li H, Yang P, Wang J, et al. HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk [J]. J Hematol Oncol, 2022, 15(1): 2. DOI: 10.1186/s13045-021-01223-x.
[30] Nieto C, Vega MA, Martín Del Valle EM. Tailored-made polydopamine nanoparticles to induce ferroptosis in breast cancer cells in combination with chemotherapy [J]. Int J Mol Sci, 2021, 22(6): 3161. DOI: 10.3390/ijms22063161.
[31] 江山,戴曦,杨小琼,等.基于铁死亡相关的lncRNA在肺鳞癌预后的分析[J].广州医药,2022,53(5):113-120, 133. DOI:10.3969/j.issn.1000-8535.2022.05.024.