铁死亡及其细胞游离亚铁原卟啉在肿瘤发生中的作用

The Role of Ferroptosis and Its Cell Free Ferrous Protoporphyrin in Tumorigenesis

摘要: 铁死亡(ferroptosis)是一种铁依赖性的调节性细胞死亡形式，由过度的脂质过氧化所引起，它与各种类型肿瘤的发生和治疗反应密切相关。然而，铁死亡性损伤(ferroptotic)可在恶性肿瘤微环境中触发炎症相关的免疫抑制，因而有利于肿瘤的生长。尽管一些研究已经发现癌症相关基因(例如RAS和TP53)的突变、与应激反应通路(stress response pathways) (如NFE2L2信号、自噬和缺氧)有关的蛋白的基因突变与上皮间质转化以及可激活铁死亡的治疗反应之间存在重要的相关性。目前铁死亡对肿瘤生物学的影响程度尚不清楚，尤其是消化道肿瘤中的铁死亡的调节机制、信号通路及其可检测的生物标志物；因此，寻找有助于检测和追踪铁死亡的生物标记物目前成为研究的热点。有研究认为，细胞游离亚铁原卟啉(cell free ferrous protoporphyrin, FH)是含亚铁原卟啉蛋白的分解产物，具有强氧化作用，导致细胞自身调节功能紊乱，与细胞癌变程度直接密切相关，目前已应用于宫颈癌、结直肠癌、尿路上皮癌等方面的检测，成为恶性肿瘤发生过程中产生的因果性生物标志因子。现就铁死亡机制及信号通路及其组织标志物细胞游离亚铁原卟啉FH在肿瘤发生中的作用作一综述，为肿瘤的诊治提供新的思路和方法。

Abstract: Ferroptosis is a form of iron-dependent regulatory cell death caused by excessive lipid peroxidation, which is closely related to the occurrence and treatment of various types of tumors. However, fer-roptotic injury can trigger inflammation-related immunosuppression in the microenvironment of malignant tumors, which is conducive to tumor growth. Although some studies have found that there is an important correlation between mutations in cancer-related genes (such as RAS and TP53), gene mutations in proteins related to stress response pathways (such as NFE2L2 signaling, autophagy, and hypoxia) and epithelial-mesenchymal transition and therapeutic responses that ac-tivate ferroptosis. At present, the effect of ferroptosis on tumor biology is not clear, especially the regulation mechanism, signaling pathway and detectable biomarkers of ferroptosis in digestive tract tumors; therefore, the search for biomarkers to help detect and track ferroptosis is currently a hot research topic. Studies have shown that cell free ferrous protoporphyrin (FH) is a decomposition product of ferrous protoporphyrin protein, which has a strong oxidation effect, leading to the disor-der of cell self-regulation function, which is directly related to the degree of cell carcinogenesis. It has been applied to the detection of cervical cancer, colorectal cancer, urothelial carcinoma and other aspects, and has become a causal biomarker factor in the process of malignant tumor. This ar-ticle reviews the mechanism and signaling pathway of ferroptosis and the role of its tissue marker cell free ferrous protoporphyrin FH in tumorigenesis, and provides new ideas and methods for the diagnosis and treatment of tumors.