摘要
近年来发现除凋亡、坏死外的一种非典型新型细胞死亡方式——细胞焦亡,其生物学特征为依赖于胱天蛋白酶(Caspases)家族蛋白切割焦孔素家族(GSDMs)蛋白,使活化的GSDMs蛋白在质膜上作用形成穿孔,导致细胞肿胀裂解,引发炎症及免疫反应。目前,有4种不同的信号途径可诱导细胞焦亡,包括经典和非经典炎性小体通路、凋亡相关Caspases介导的通路和基于颗粒酶的焦亡通路。在这些信号通路中,GSDMs蛋白是最终的细胞焦亡执行者。细胞焦亡与肿瘤细胞死亡及正常组织炎性损伤密切相关,近年的研究发现,适度的细胞焦亡会导致肿瘤细胞死亡,发挥抗肿瘤作用,同时刺激肿瘤免疫微环境;而细胞焦亡不当激活又可促进肿瘤发展。药物抗肿瘤治疗中,如肿瘤免疫治疗、化疗、靶向治疗等手段发挥了较好的抗肿瘤作用,但仍存在耐药、复发、损伤正常组织等不足,而最新的研究表明多种天然药物成分具有通过介导焦亡途径的抗肿瘤作用及辅助抗肿瘤作用,且有多靶点和多通路的特点,这为抗肿瘤治疗的研究提供了新的思路和方法。笔者对细胞焦亡的分子机制、焦亡在肿瘤及肿瘤免疫微环境中的调控作用进行综述,同时重点对调控细胞焦亡的相关天然药物成分在抗肿瘤治疗中的新近研究进行总结,以期为基于细胞焦亡的抗肿瘤治疗与研究提供思路。
In recent years,pyroptosis,an atypical new cell death mode other than apoptosis and necrosis,has been discovered.The biological feature of pyroptosis is that it depends on the cleavage of gasdermin family(GSDMs)by caspases family proteins.The activated GSDMs protein acts on the plasma membrane to form a perforation,resulting in cell swelling and lysis,triggering inflammation and immune response.Currently,there are four distinct signaling pathways that induce pyroptosis,including canonical and non-canonical inflammasome pathways,apoptosis-associated caspases-mediated pathways,and granzyme-based pyroptosis pathways.Among these signaling pathways,GSDMs are the ultimate pyroptotic executors.Pyroptosis is closely related to tumor cell death and normal tissue inflammatory damage.Recent studies have found that moderate pyroptosis can lead to tumor cell death,exert an anti-tumor effect,and stimulate the tumor immune microenvironment at the same time;It can also promote tumor development.In drug anti-tumor therapy,such as tumor immunotherapy,chemotherapy,targeted therapy and other means have played a good anti-tumor effect,but there are still some shortcomings such as drug resistance,recurrence,and damage to normal tissues.The latest research shows that a variety of natural drugs components have anti-tumor effects and auxiliary anti-tumor effects through the mediating pyroptosis pathway,and have the characteristics of multiple targets and multiple pathways,which provide new ideas and methods for the study of anti-tumor therapy.The author reviews the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment.At the same time,the author summarizes the recent research on the related natural medicinal components regulating pyroptosis in anti-tumor therapy,with a view to providing Provides ideas for anti-tumor therapy and research based on pyroptosis.
作者
陈卓
陆露
方兴刚
郭兴荣
罗杰
CHEN Zhuo;LU Lu;FANG Xinggang;GUO Xingrong;LUO Jie(Clinical College of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Key Laboratory of Embryonic Stem Cell Research,Shiyan 442099,China;Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,Shiyan 442099,China;Taihe Hospital,Doctoral Training Unit of Hubei University of Chinese Medicine,Shiyan 442099,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2023年第14期226-238,共13页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(82073232)
国家自然科学基金项目(81671831)
湖北省引进国外人才和智力项目(Yz2020015)
湖北省卫生健康委青年人才项目(WJ2021F032)。
作者简介
第一作者:陈卓,博士,中西医结合治疗脑病的相关研究,E-mail:chenzhuo2020tougao@163.com;通信作者:罗杰,教授,主任医师,博士生导师,从事脑病、脑肿瘤的防治研究,E-mail:luojie2022tougao@163.com。
