国际口腔医学杂志

国际口腔医学杂志 ›› 2024, Vol. 51 ›› Issue (1): 36-44.doi: 10.7518/gjkq.2024006

• 口腔肿瘤学专栏 • 上一篇    下一篇

铁死亡在口腔疾病中的研究进展

傅豫(),何薇,黄兰()   

  1. 重庆医科大学附属口腔医院正畸科 口腔疾病与生物医学重庆市重点实验室重庆市高校市级口腔生物医学工程重点实验室 重庆 401147
  • 收稿日期:2023-04-23 修回日期:2023-08-30 出版日期:2024-01-01 发布日期:2024-01-10
  • 通讯作者: 黄兰
  • 作者简介:傅豫，硕士，Email：<email>2022120653@stu.cqmu.edu.cn</email>
  • 基金资助:
    国家自然科学基金(82170989);重庆市自然科学基金(CSTB2022NSCQ-MSX0794)

Ferroptosis and its implication in oral diseases

Fu Yu(),He Wei,Huang Lan()   

  1. Dept. of Orthodontics, Stomatological Hospital of Chongqing Medical University & Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences & Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
  • Received:2023-04-23 Revised:2023-08-30 Online:2024-01-01 Published:2024-01-10
  • Contact: Lan Huang
  • Supported by:
    National Natural Science Foundation of China(82170989);Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX0794)

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摘要：

铁死亡是一种可调控的，具有铁依赖性的，由脂质过氧化驱动的细胞死亡形式，是一种重要的细胞死亡形式，在多种疾病中发挥着重要作用。目前铁死亡在癌症、缺血/再灌注损伤疾病、各类神经退行性疾病等方面的研究取得了一定的成果，在口腔疾病中的作用也越来越受关注。铁死亡是口腔癌的新兴治疗靶点。许多炎症损伤疾病与铁死亡相关，牙周炎作为一种慢性炎症性疾病，与铁死亡的发生过程可能存在一定的相关性。本文就目前铁死亡与口腔疾病的相关研究及发现进行综述，旨在为探索口腔疾病的发病机制和诊疗提供参考。

关键词: 铁死亡, 口腔疾病, 口腔癌, 牙周炎, 肿瘤治疗

Abstract:

Ferroptosis is a regulated, iron-dependent form of cell death driven by lipid peroxidation and plays an important role in a variety of diseases. It has been studied in cancer, ischemia/reperfusion injury diseases, and neurodegenerative diseases. As an important form of cell death, ferroptosis has received increasing attention in oral disease research. Some advances have been achieved in related studies. Ferroptosis has become an emerging therapeutic target for oral cancer and has been associated with many inflammatory injury diseases. As a chronic inflammatory disease, periodontitis may have some correlation with ferroptosis. This work reviews current findings on ferroptosis to provide a reference for the mechanism, diagnosis, and treatment of related oral diseases.

Key words: ferroptosis, oral disease, oral cancer, periodontitis, cancer therapy

中图分类号: 

  • R782.4

表 1

OSCC靶向治疗有关的铁死亡研究"

干预/靶向基因OSCC细胞系/组织样本相关表现参考文献
鼠尾草酸、Nrf2/HO-1/xCT途径SCC9-DDP和 CAL27-DDP 细胞（顺铂抵抗细胞）用鼠尾草酸处理顺铂耐药的OSCC细胞会降低GSH水平，增加ROS和脂质过氧化水平；这种作用可被liproxstatin-1逆转[13]
奎诺司他（quisinostat）CAL-27和TCA-8113细胞细胞的线粒体缩小且萎缩，线粒体嵴减少甚至缺失，线粒体膜密度增加，细胞内ROS水平增加，GPX4下调[14]
大黄根酚（chrysophanol）FaDu和SAS细胞ROS积聚，GPX4水平降低[15]
非热等离子体（non-thermal plasma）SAS和Ca9-22细胞细胞内发生了脂质过氧化，细胞内ROS水平、线粒体内ROS水平升高；非热等离子体所致的癌细胞死亡可被事先应用的FAC所促进，并被DFO所抑制[16]
PDT加Ce6-ErastinCAL-27 细胞细胞内ROS过度积聚，氧浓度增加，SLC7A11表达受到抑制[17]
circFNDC3B、miR-520d-5p32份 OSCC 样本，CAL27 和SCC15细胞系通过shRNA沉默circFNDC3B可以抑制GPX4和SLC7A11的表达，增强OSCC细胞中的ROS、铁和Fe（Ⅱ）水平；CircFNDC3B敲除加强了Erastin诱导的对OSCC细胞的生长抑制作用[19]
EZH2、SLC7A11、MiR-125b-5p20份TSCC样本，SCC9和CAL27细胞系EZH2和SLC7A11过量表达抑制了Erastin诱导的TSCC细胞的铁死亡，伴丙二醛水平和Fe（Ⅱ）水平降低[20]
miR-34c-3p43份OSCC样本，SCC-25和CAL27细胞miR34c-3p过表达使细胞中的ROS、丙二醛、Fe（Ⅱ）水平上升，GSH和GPX4水平降低，且可被Fer-1抑制[21]
PER1OSCC，SCC15 和CAL27 细胞系过表达PER1，GPX4、SLC7A11和GSH水平降低，运铁蛋白受体、丙二醛、ROS和Fe（Ⅱ）水平升高，线粒体皱缩，膜密度增加，线粒体嵴减少；沉默PER1，GPX4、SLC7A11和GSH水平升高，运铁蛋白受体、丙二醛、ROS和Fe（Ⅱ）水平降低，线粒体无明显形态学改变[22]
IL-6/STAT3/xCT129份HNSCC样本，12份黏膜白斑病样本，HN4和CAL27细胞沉默xCT，细胞线粒体皱缩，线粒体嵴减少；细胞内Fe（Ⅱ）增多，脂质过氧化水平增加，GSH水平降低[23]
AEBP1CAL27，SCC15和CAR（顺铂耐药细胞）细胞系沉默AEBP1增强了由SSZ诱导的细胞内ROS、游离铁、丙二醛表达水平升高，FTH1、GPX4和SLC7A11表达水平降低，环氧合酶2表达水平升高[24]
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