细胞焦亡在肺癌药物治疗及预后中的作用机制

Mechanisms of pyroptosis in drug therapy and prognosis of lung cancer

细胞焦亡(pyroptosis)作为近年来新发现的一种依赖半胱氨酸蛋白酶-1(caspase-1)的细胞溶解性死亡,是由gasdermin蛋白介导的一种高度促炎性的程序性细胞死亡方式,主要机制涉及依赖caspase-1的经典途径和依赖caspase-4/5/11的非经典途径。多种化合物能够在肺癌中通过影响NF-κB信号通路、NLRP3炎症小体、GSDMD/caspase-1/IL-18/IL-1β以及GSDME/caspase-3等途径调控细胞焦亡发挥抗肿瘤作用,从而为开发药物提供理论依据。而且,多种与细胞焦亡相关的基因和蛋白质能够影响肺癌患者的预后,并作为肺癌的独立预后标志物。本文围绕细胞焦亡在肺癌药物治疗和预后中的作用机制的最新研究进行综述,旨在为基于细胞焦亡的肺癌临床治疗提供参考。

Pyroptosis is a newly discovered cellular lytic necrosis depending on caspase-1.It is a highly proinflammatory mode of programmed cell death mediated by gasdermin proteins.Its main mechanism involves in caspase-1-dependent canonical pathway and caspase-4/5/11-dependent non-canonical pathway.It is found that multiple compounds may play a role in anti-lung cancer by affecting NF-κB signaling pathway,NLRP3inflammasomes,GSDMD/caspase-1/IL-1β/IL-18 and GSDME/caspase-3 to regulate the pyroptosis,thus providing a theoretical basis for drug research and development.Moreover,the multiple genes and proteins associated with pyroptosis are able to influence the prognosis of patients with lung cancer and serve as independent prognostic markers for lung cancer.This paper reviews the latest research on the mechanisms of pyroptosis in drug treatment and prognosis of lung cancer,which will contribute to the clinical treatment of lung cancer based on pyroptosis.