细胞焦亡的分子机制及其在肿瘤治疗中的应用  

Molecular mechanism of pyroptosis and its application in the treatment of tumor

作　　者：龚晓文(综述) 梁超杰(审校)[2] GONG Xiaowen;LIANG Chaojie(First Clinical Medical College,Shanxi Medical University,Taiyuan 030001;Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一临床医学院,太原030001 [2]山西医科大学第一医院肝胆胰外科及肝脏移植中心,太原030001

出　　处：《临床与病理杂志》2023年第9期1690-1697,共8页Journal of Clinical and Pathological Research

基　　金：山西省应用基础研究计划项目(201901D211480)。

摘　　要：细胞焦亡是一种溶解性促炎类型的程序性细胞死亡,在各种炎症性疾病模型中被广泛研究。裂解的Gasdermin家族成员诱导的膜穿孔和细胞肿胀是细胞焦亡的主要特征。细胞焦亡主要有经典的caspase-1依赖性和非caspase-1依赖性途径2种分子机制,二者都会导致细胞的肿胀和促炎性细胞因子白介素(interleukin,IL)-1β和IL-18释放,扩大局部或全身的炎症。细胞焦亡与肿瘤之间关系复杂。一方面,细胞焦亡可以构建有利于肿瘤细胞增殖的微环境,加快肿瘤进展;另一方面,细胞焦亡的过度激活可以抑制肿瘤细胞的进展。通过调控Gasdermin家族成员、炎症小体等细胞焦亡相关因素的表达可以诱导靶细胞发生细胞焦亡,从而达到治疗非小细胞肺癌、胃癌、结直肠癌、肝细胞癌、白血病和宫颈癌等肿瘤的目的。探讨细胞焦亡在肿瘤治疗中的作用,对开发肿瘤治疗新策略的研究具有重要意义。Pyroptosis,a lytic pro-inflammatory type of programmed cell death,has been widely studied in diverse models of inflammatory diseases.Membrane perforation and cell swelling induced by cleaved Gasdermin family members is the main characteristic of pyroptosis.There are 2 main molecular mechanisms of pyroptosis:the classical caspase-1-dependent pathway and the non-caspase-1-dependent pathway.Both pathways lead to cell swelling and the release of pro-inflammatory cytokines interleukin(IL)-1βand IL-18,and expand local or systemic inflammation.The relationship between pyroptosis and tumors is complex.On one hand,pyroptosis can build a microenvironment conducive to tumor cell proliferation and accelerate tumor progression.On the other hand,overactivation of pyroptosis can inhibit the progression of tumor cells.Inducing target cells to undergo pyroptosis by regulating the expression of Gasdermin family member,inflammasomes,and other pyroptosis-related factors can be a therapeutic method for various cancers,such as non-small cell lung cancer,gastric cancer,colorectal cancer,hepatocellular carcinoma,leukemia,and cervical cancer.Exploring the role of pyroptosis in tumor therapy is of great significance for the development of novel strategies in tumor treatment.

关 键 词：细胞焦亡 肿瘤 CASPASE家族 Gasdermin家族 

分 类 号：R730[医药卫生—肿瘤]