细胞焦亡的分子机制及其与恶性肿瘤的关系

细胞焦亡是细胞程序性死亡方式之一,可由caspase-1、caspase-3、caspase-4、caspase-5、caspase-8、caspase-11介导,主要分为经典和非经典两条通路,炎性小体在其中发挥重要作用。消皮素D是焦亡的重要底物,经酶剪切后释放出氨基端片段,在细胞膜上形成小孔,导致细胞渗透性溶解并释放细胞内容物,引起炎症反应。焦亡通路的各种成分与肿瘤的发生、侵袭和转移有关,关于焦亡的研究开拓了肿瘤治疗的新领域。本文总结了近年来有关焦亡分子机制的研究进展,影响肿瘤发生发展的焦亡相关分子,以及焦亡在化疗药物抗癌治疗中的应用与前景。

Molecular mechanism of pyroptosis and its relationship with malignant tumors

Pyroptosis is a form of programmed cell death, and can be mediated by caspase-1, caspase-3, caspase-4, caspase-5, caspase-8, and caspase-11. It is primarily induced through two pathways in which inflammasomes play an important role: the canonical and non-canonical pathways. Gasdermin D is a critical substrate for pyroptosis. Following enzymatic cleavage, gasdermin D releases Nterminal fragments that generate pores on the plasma membrane. This causes osmotic lysis and ultimately, the release of cytosolic content which consequently induces inflammatory responses. Various intermediaries of the pyroptotic cell death pathways are involved in cancer initiation, invasion and metastasis; hence, the research on pyroptosis exploits a new field of cancer treatment. In this review, we summarize the recent progresses in research focused on elucidating the molecular mechanism of pyroptosis, discovering the effects of pyroptotic-related molecules on the initiation and progression of cancer, and the applications and prospects of targeting pyroptosis for cancer treatments based specifically on the development of chemotherapy drugs.