|
|
铁代谢异常与卵巢癌相关研究进展
|
Abstract:
卵巢癌具有较高的发病率及病死率，严重威胁全世界女性的健康。铁是人体必须微量元素，参与许多细胞生理过程，研究证实肿瘤细胞对铁表现为强烈的依赖，过表达铁代谢相关的蛋白质，这使得铁在肿瘤细胞内蓄积，导致其快速增殖。近年来，铁代谢在卵巢癌中发生发展的作用机制是研究的热点问题。本篇综述讨论了铁代谢异常与卵巢癌的关系，了解铁与铁代谢相关产物在卵巢癌细胞中的变化，为指导卵巢癌的诊治提供一种新的诊疗思路。
Ovarian cancer has a high incidence rate and mortality, which seriously threatens the health of women all over the world. Iron is an essential trace element for the human body and participates in many cellular physiological processes. Studies have shown that tumor cells exhibit a strong dependence on iron and overexpress proteins related to iron metabolism, leading to the accumulation of iron in tumor cells and rapid proliferation. In recent years, the mechanism of iron metabolism in the occurrence and development of ovarian cancer has been a hot research topic. This review discusses the relationship between abnormal iron metabolism and ovarian cancer, understanding the changes in iron and iron metabolism related products in ovarian cancer cells, and providing a new diagnostic and therapeutic approach for guiding the diagnosis and treatment of ovarian cancer.
| [1] | Shayeghi, M., Latunde-Dada, G.O., Oakhill, J.S., Laftah, A.H., Takeuchi, K., Halliday, N., et al. (2005) Identification of an Intestinal Heme Transporter. Cell, 122, 789-801. https://doi.org/10.1016/j.cell.2005.06.025 |
| [2] | Shesh, B. and Connor, J.R. (2023) A Novel View of Ferritin in Cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1878, Article 188917. https://doi.org/10.1016/j.bbcan.2023.188917 |
| [3] | Wang, Y., Zhang, J., Su, Y., Shen, Y., Jiang, D., Hou, Y., et al. (2020) Author Correction: G9a Regulates Breast Cancer Growth by Modulating Iron Homeostasis through the Repression of Ferroxidase Hephaestin. Nature Communications, 11, Article No. 3789. https://doi.org/10.1038/s41467-020-17413-z |
| [4] | Chung, J.W., Shin, E., Kim, H., Han, H., Cho, J.Y., Choi, Y.R., et al. (2017) Hepatic Iron Overload in the Portal Tract Predicts Poor Survival in Hepatocellular Carcinoma after Curative Resection. Liver International, 38, 903-914. https://doi.org/10.1111/liv.13619 |
| [5] | Buranrat, B. and Connor, J.R. (2015) Cytoprotective Effects of Ferritin on Doxorubicin-Induced Breast Cancer Cell Death. Oncology Reports, 34, 2790-2796. https://doi.org/10.3892/or.2015.4250 |
| [6] | Salatino, A., Aversa, I., Battaglia, A.M., Sacco, A., Di Vito, A., Santamaria, G., et al. (2019) H-Ferritin Affects Cisplatin-Induced Cytotoxicity in Ovarian Cancer Cells through the Modulation of ROS. Oxidative Medicine and Cellular Longevity, 2019, Article ID: 3461251. https://doi.org/10.1155/2019/3461251 |
| [7] | Sukiennicki, G.M., Marciniak, W., Muszyńska, M., Baszuk, P., Gupta, S., Białkowska, K., et al. (2019) Iron Levels, Genes Involved in Iron Metabolism and Antioxidative Processes and Lung Cancer Incidence. PLOS ONE, 14, e0208610. https://doi.org/10.1371/journal.pone.0208610 |
| [8] | Bian, Z., Hann, H.-W., Ye, Z., Yin, C., Wang, Y., Fang, W., et al. (2018) Ferritin Level Prospectively Predicts Hepatocarcinogenesis in Patients with Chronic Hepatitis B Virus Infection. Oncology Letters, 16, 3499-3508. https://doi.org/10.3892/ol.2018.9099 |
| [9] | Wang, F., Xu, W., Zhang, W., Xu, R., Sun, J., Zhang, G., et al. (2023) Transferrin Receptor 1 Promotes Hepatocellular Carcinoma Progression and Metastasis by Activating the mTOR Signaling Pathway. Hepatology International, 18, 636-650. https://doi.org/10.1007/s12072-023-10607-9 |
| [10] | Adachi, M., Kai, K., Yamaji, K., Ide, T., Noshiro, H., Kawaguchi, A., et al. (2019) Transferrin Receptor 1 Overexpression Is Associated with Tumour De‐Differentiation and Acts as a Potential Prognostic Indicator of Hepatocellular Carcinoma. Histopathology, 75, 63-73. https://doi.org/10.1111/his.13847 |
| [11] | Kim, H., Villareal, L.B., Liu, Z., Haneef, M., Falcon, D.M., Martin, D.R., et al. (2023) Transferrin Receptor‐Mediated Iron Uptake Promotes Colon Tumorigenesis. Advanced Science, 10, Article ID: 2207693. https://doi.org/10.1002/advs.202207693 |
| [12] | Fang, X., Hu, P., Gao, Y., Chen, C. and Xu, J. (2023) Transferrin Receptor Modulated by MicroRNA-497-5p Suppresses Cervical Cancer Cell Malignant Phenotypes. Advances in Clinical and Experimental Medicine, 33, 273-282. https://doi.org/10.17219/acem/168342 |
| [13] | Zhang, Q., Chen, C., Zou, X., Wu, W., Di, Y., Li, N., et al. (2024) Iron Promotes Ovarian Cancer Malignancy and Advances Platinum Resistance by Enhancing DNA Repair via FTH1/FTL/POLQ/RAD51 Axis. Cell Death & Disease, 15, Article No. 329. https://doi.org/10.1038/s41419-024-06688-5 |
| [14] | Liu, B., Song, Z., Fan, Y., Zhang, G., Cao, P., Li, D., et al. (2021) Downregulation of FPN1 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Lung Cancer. Aging, 13, 8737-8761. https://doi.org/10.18632/aging.202685 |
| [15] | Chen, Y., Zhang, Z., Yang, K., Du, J., Xu, Y. and Liu, S. (2014) Myeloid Zinc-Finger 1 (MZF-1) Suppresses Prostate Tumor Growth through Enforcing Ferroportin-Conducted Iron Egress. Oncogene, 34, 3839-3847. https://doi.org/10.1038/onc.2014.310 |
| [16] | Wang, L., Liu, X., You, L., Ci, Y., Chang, S., Yu, P., et al. (2018) Hepcidin and Iron Regulatory Proteins Coordinately Regulate Ferroportin 1 Expression in the Brain of Mice. Journal of Cellular Physiology, 234, 7600-7607. https://doi.org/10.1002/jcp.27522 |
| [17] | Basuli, D., Tesfay, L., Deng, Z., Paul, B., Yamamoto, Y., Ning, G., et al. (2017) Iron Addiction: A Novel Therapeutic Target in Ovarian Cancer. Oncogene, 36, 4089-4099. https://doi.org/10.1038/onc.2017.11 |
| [18] | Winterbourn, C.C. (1995) Toxicity of Iron and Hydrogen Peroxide: The Fenton Reaction. Toxicology Letters, 82, 969-974. https://doi.org/10.1016/0378-4274(95)03532-x |
| [19] | Ichijo, H., Nishida, E., Irie, K., Dijke, P.t., Saitoh, M., Moriguchi, T., et al. (1997) Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and P38 Signaling Pathways. Science, 275, 90-94. https://doi.org/10.1126/science.275.5296.90 |
| [20] | Han, B., Zheng, R., Zeng, H., Wang, S., Sun, K., Chen, R., et al. (2024) Cancer Incidence and Mortality in China, 2022. Journal of the National Cancer Center, 4, 47-53. https://doi.org/10.1016/j.jncc.2024.01.006 |
| [21] | Lheureux, S., Gourley, C., Vergote, I. and Oza, A.M. (2019) Epithelial Ovarian Cancer. The Lancet, 393, 1240-1253. https://doi.org/10.1016/s0140-6736(18)32552-2 |
| [22] | 中国抗癌协会妇科肿瘤专业委员会. 卵巢恶性肿瘤诊断与治疗指南(2021年版) [J]. 中国癌症杂志, 2021, 31(6): 490-500. |
| [23] | Rockfield, S., Raffel, J., Mehta, R., Rehman, N. and Nanjundan, M. (2017) Iron Overload and Altered Iron Metabolism in Ovarian Cancer. Biological Chemistry, 398, 995-1007. https://doi.org/10.1515/hsz-2016-0336 |
| [24] | Huang, Y., Huang, J., Huang, Y., Gan, L., Long, L., Pu, A., et al. (2020) TFRC Promotes Epithelial Ovarian Cancer Cell Proliferation and Metastasis via Up-Regulation of AXIN2 Expression. American Journal of Cancer Research, 10, 131-147. |
| [25] | Rafati Rahimzadeh, M., Rafati Rahimzadeh, M., Kazemi, S., Moghadamnia, A.R., Ghaemi Amiri, M. and Moghadamnia, A.A. (2023) Iron; Benefits or Threatens (with Emphasis on Mechanism and Treatment of Its Poisoning). Human & Experimental Toxicology, 42. https://doi.org/10.1177/09603271231192361 |
| [26] | Li, D., Zhang, M. and Chao, H. (2021) Significance of Glutathione Peroxidase 4 and Intracellular Iron Level in Ovarian Cancer Cells— “Utilization” of Ferroptosis Mechanism. Inflammation Research, 70, 1177-1189. https://doi.org/10.1007/s00011-021-01495-6 |
| [27] | 武福文, 洪莉. 铁死亡在卵巢癌中的机制探究[J]. 中国计划生育和妇产科, 2023, 15(7): 3-5, 13. |
| [28] | The Cancer Genome Atlas Research Network (2011) Integrated Genomic Analyses of Ovarian Carcinoma. Nature, 474, 609-615. https://doi.org/10.1038/nature10166 |
| [29] | Xu, R., Wang, W. and Zhang, W. (2023) Ferroptosis and the Bidirectional Regulatory Factor P53. Cell Death Discovery, 9, Article No. 197. https://doi.org/10.1038/s41420-023-01517-8 |
| [30] | Wang, Y., Hu, M., Cao, J., Wang, F., Han, J.R., Wu, T.W., et al. (2025) ACSL4 and Polyunsaturated Lipids Support Metastatic Extravasation and Colonization. Cell, 188, 412-429.E27. https://doi.org/10.1016/j.cell.2024.10.047 |
| [31] | Kobayashi, (2010) Clear Cell Carcinoma of the Ovary: Potential Pathogenic Mechanisms (Review). Oncology Reports, 23, 1193-1203. https://doi.org/10.3892/or_00000750 |
| [32] | Shigetomi, H., Imanaka, S. and Kobayashi, H. (2021) Effects of Iron-Related Compounds and Bilirubin on Redox Homeostasis in Endometriosis and Its Malignant Transformations. Hormone Molecular Biology and Clinical Investigation, 43, 187-192. https://doi.org/10.1515/hmbci-2021-0065 |
| [33] | Lobello, N., Biamonte, F., Pisanu, M.E., Faniello, M.C., Jakopin, Ž., Chiarella, E., et al. (2016) Ferritin Heavy Chain Is a Negative Regulator of Ovarian Cancer Stem Cell Expansion and Epithelial to Mesenchymal Transition. Oncotarget, 7, 62019-62033. https://doi.org/10.18632/oncotarget.11495 |
| [34] | Zhao, J., Guo, N., Zhang, L. and Wang, L. (2018) Serum CA125 in Combination with Ferritin Improves Diagnostic Accuracy for Epithelial Ovarian Cancer. British Journal of Biomedical Science, 75, 66-70. https://doi.org/10.1080/09674845.2017.1394051 |
| [35] | 刘玉娇, 宋公青, 周志红. 血清癌胚抗原、甲胎蛋白、糖类抗原125及铁蛋白联合检测在卵巢癌诊断中的应用研究[J]. 临床医学工程, 2023, 30(7): 935-936. |
| [36] | Kapper, C., Oppelt, P., Arbeithuber, B., Gyunesh, A.A., Vilusic, I., Stelzl, P., et al. (2024) Targeting Ferroptosis in Ovarian Cancer: Novel Strategies to Overcome Chemotherapy Resistance. Life Sciences, 349, Article 122720. https://doi.org/10.1016/j.lfs.2024.122720 |
| [37] | 周炜程, 李锐, 张亮, 等. 基于类芬顿反应构建磁性纳米粒治疗卵巢癌: 体外实验[J]. 中国医学影像技术, 2021, 37(6): 830-835. |
| [38] | Shi, Z., Yuan, H., Cao, L. and Lin, Y. (2023) AKT1 Participates in Ferroptosis Vulnerability by Driving Autophagic Degradation of FTH1 in Cisplatin-Resistant Ovarian Cancer. Biochemistry and Cell Biology, 101, 422-431. https://doi.org/10.1139/bcb-2022-0361 |
| [39] | Lopes-Coelho, F., Gouveia-Fernandes, S., Gonçalves, L.G., Nunes, C., Faustino, I., Silva, F., et al. (2015) HNF1β Drives Glutathione (GSH) Synthesis Underlying Intrinsic Carboplatin Resistance of Ovarian Clear Cell Carcinoma (OCCC). Tumor Biology, 37, 4813-4829. https://doi.org/10.1007/s13277-015-4290-5 |
| [40] | Zhou, H., Chen, X., Cai, L., Nan, X., Chen, J., Chen, X., et al. (2019) Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer. Frontiers in Oncology, 9, Article 1398. https://doi.org/10.3389/fonc.2019.01398 |
| [41] | Hong, T., Lei, G., Chen, X., Li, H., Zhang, X., Wu, N., et al. (2021) PARP Inhibition Promotes Ferroptosis via Repressing SLC7A11 and Synergizes with Ferroptosis Inducers in BRCA-Proficient Ovarian Cancer. Redox Biology, 42, Article 101928. https://doi.org/10.1016/j.redox.2021.101928 |
| [42] | Sandoval, T.A., Salvagno, C., Chae, C., Awasthi, D., Giovanelli, P., Marin Falco, M., et al. (2024) Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer. Cancer Discovery, 14, 1901-1921. https://doi.org/10.1158/2159-8290.cd-23-1451 |
| [43] | Wu, J., Bao, L., Zhang, Z. and Yi, X. (2017) Nrf2 Induces Cisplatin Resistance via Suppressing the Iron Export Related Gene SLC40A1 in Ovarian Cancer Cells. Oncotarget, 8, 93502-93515. https://doi.org/10.18632/oncotarget.19548 |
