细胞焦亡在癌症发生发展及治疗中作用的研究进展

Roles of pyroptosis in occurrence,development and treatment of cancer:a review

细胞焦亡是一种炎性程序性细胞死亡模式,主要由活化的胱天蛋白酶1/4/5/11和gasdermin(GSDM)家族蛋白介导发生。炎症小体激活后,一方面活化的胱天蛋白酶1/4/5/11能促使炎症因子活化,同时还能切割GSDM家族蛋白产生N端片段,并随后转移至细胞膜并形成孔道,加速炎症因子释放的同时还引起细胞肿胀破裂死亡。近年来研究表明,细胞焦亡与肺癌、胃癌、肝癌、结直肠癌和乳腺癌等多种癌症的发生发展及治疗密切相关。一方面,炎症小体过度激活所致的炎症反应促进癌症的发生发展;另一方面,缺失细胞焦亡功能的细胞更易向癌细胞转变;同时,靶向癌细胞诱导其发生细胞焦亡可有效杀伤癌细胞。细胞焦亡与癌症的关系十分复杂。本文就细胞焦亡的发生机制及其在多种癌症发生和治疗中的作用机制进行综述,为癌症治疗和药物研发提供参考。

Pyroptosis is a mode of inflammatory programmed cell death that is mainly mediated by activated caspase1/4/5/11 and gasdermin(GSDM)family proteins.Upon activation of inflammasome,activated caspase 1/4/5/11 can promote the maturation of inflammatory factors and cleave GSDM family proteins to generate N-terminal fragments,which are subsequently translocated to the cel membrane and form pores,accelerating the release of inflammatory factors and causing cell swelling,rupture and death.Recent studies have shown that pyroptosis is closely related to the occurrence,development and treatment of such cancers as lung cancer,gastric cancer,liver cancer,colorectal cancer,and breast cancer.On the one hand,the inflammatory response caused by the excessive activation of inflammasomes promotes the occurrence and development of cancer.On the other hand,cells lacking pyroptotic function are more likely to be transformed into cancer cells.However,targeting cancer cells to induce pyroptosis can effectively kill cancer cells.The relationship between pyroptosis and cancer is complex,and this paper reviews the mechanisms of pyroptosis and its role in the occurrence,development and treatment of various cancers to provide reference for cancer treatment and drug development.