铁死亡与宫颈癌相关性的研究进展

doi:10.12280/gjszjk.20230120

摘要/Abstract

摘要：

铁死亡是一种新形式的调节性细胞死亡，其特征是脂质过氧化物的铁依赖性积累，该过程受多种途径调节，包括谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）途径、铁代谢和脂质代谢途径。铁死亡在各种生理和病理过程中起着关键作用，如组织稳态、癌症和神经变性。宫颈癌是全球女性第四大常见癌症，死亡率高。铁死亡可能参与宫颈癌的发病机制，并可能作为一个潜在的治疗及预后靶点。研究表明，抑制GPX4、铁螯合和调节脂质代谢途径可以诱导宫颈癌细胞的铁死亡。此外，一些天然化合物和药物已被证明可诱导宫颈癌细胞的铁死亡，具有作为宫颈癌治疗剂的潜力。研究铁死亡的机制及其调控途径，可能为宫颈癌治疗策略的开发提供新的见解。

关键词: 宫颈肿瘤, 铁死亡, 磷脂氢过氧化物谷胱甘肽过氧化物酶, 谷胱甘肽, 活性氧, 治疗, 预后

Abstract:

Ferroptosis as a new form of regulatory cell death is characterized by iron-dependent accumulation of lipid peroxides. Ferroptosis is regulated by many pathways, including glutathione peroxidase 4 (GPX4) pathway, iron metabolism and lipid metabolism pathway. Ferroptosis plays a key role in various physiological and pathological processes, such as tissue homeostasis, cancer and neurodegeneration. Cervical cancer is the fourth most common cancer among women in the world, with high mortality. Ferroptosis may be involved in the pathogenesis of cervical cancer, and that ferroptosis may be a potential therapeutic and prognostic target. Studies show that the inhibition of GPX4 and iron chelation, and the regulation of lipid metabolism pathway, can induce the ferroptosis of cervical cancer cells. In addition, some natural compounds and drugs have been proved to induce the ferroptosis of cervical cancer cells, indicating their potential as therapeutic agents for cervical cancer. Studying the mechanism and regulation of ferroptosis may provide new insights for the new treatment strategies of cervical cancer.

Key words: Uterine cervical neoplasms, Ferroptosis, Phospholipid hydroperoxide glutathione peroxidase, Glutathione, Reactive oxygen species, Therapy, Prognosis

高亚婷, 马建红, 马怡彤, 刘畅. 铁死亡与宫颈癌相关性的研究进展[J]. 国际生殖健康/计划生育杂志, 2023, 42(5): 436-440.

GAO Ya-ting, MA Jian-hong, MA Yi-tong, LIU Chang. Progress on the Relationship between Ferroptosis and Cervical Cancer[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(5): 436-440.

图/表 1

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药物	机制	治疗方向
ACSL4	催化长链脂肪酸激活的关键酶，与多种生物反应密切相关，包括炎症反应、细胞死亡和免疫激活反应等	可以缩小宫颈癌癌灶体积，是肿瘤治疗的潜在靶点和生物标志物^[24]
OA	抑制肿瘤生长，增加肿瘤细胞Fe²⁺和ROS的积累，促进细胞铁死亡	OA作为ACSL4的天然激活剂，可增强其在宫颈癌中的抗癌作用^[25]
Nrf2	调节抗氧化应激信号通路，在多种癌症中通过激活铁代谢及GSH代谢相关基因和ROS解毒酶抑制铁死亡	脯氨酰异构酶1（prolyl isomerase 1）通过Nrf2/GPX4轴影响宫颈癌细胞的铁死亡和对铂类药物的敏感性，是宫颈癌的潜在治疗靶点^[26]
Cdc25	Cdc25/丙酮酸激酶M2/受体酪氨酸蛋白激酶ErbB-2（Cdc25/pyruvate kinase M2/receptor tyrosine-protein kinase ErbB-2，Cdc25/PKM2/ErbB2）轴抑制宫颈癌细胞铁死亡	通过抑制宫颈癌细胞铁死亡，增加癌细胞对放疗的抗性^[27]

药物	机制	治疗方向
ACSL4	催化长链脂肪酸激活的关键酶，与多种生物反应密切相关，包括炎症反应、细胞死亡和免疫激活反应等	可以缩小宫颈癌癌灶体积，是肿瘤治疗的潜在靶点和生物标志物^[24]
OA	抑制肿瘤生长，增加肿瘤细胞Fe²⁺和ROS的积累，促进细胞铁死亡	OA作为ACSL4的天然激活剂，可增强其在宫颈癌中的抗癌作用^[25]
Nrf2	调节抗氧化应激信号通路，在多种癌症中通过激活铁代谢及GSH代谢相关基因和ROS解毒酶抑制铁死亡	脯氨酰异构酶1（prolyl isomerase 1）通过Nrf2/GPX4轴影响宫颈癌细胞的铁死亡和对铂类药物的敏感性，是宫颈癌的潜在治疗靶点^[26]
Cdc25	Cdc25/丙酮酸激酶M2/受体酪氨酸蛋白激酶ErbB-2（Cdc25/pyruvate kinase M2/receptor tyrosine-protein kinase ErbB-2，Cdc25/PKM2/ErbB2）轴抑制宫颈癌细胞铁死亡	通过抑制宫颈癌细胞铁死亡，增加癌细胞对放疗的抗性^[27]