NLRP3炎性小体诱导的焦亡及其在肿瘤中的作用

The Pyroptosis Induced by NLRP3 Inflammasome and Its Role in Tumor

程序性细胞死亡(PCD)是指细胞通过基因编码方式发生了自发性细胞死亡,包括凋亡、焦亡、自噬、坏死性凋亡(又称程序性坏死) 4种方式,其中焦亡是近期发现的一种全新的程序性细胞死亡模式。与凋亡不同,焦亡通过诱导细胞膜上膜孔的形成,引起细胞外炎症反应。目前已经发现了4种焦亡诱导途径。诱导焦亡发生需要多个细胞因子的介导,而炎性小体是大多数焦亡激活途径所必需的。炎性小体是一种多聚体蛋白质复合物,其中NOD样受体蛋白3(NLRP3)炎性小体是目前研究较为深入的一种炎性小体,它在不同类型的肿瘤中介导焦亡的发生。NLRP3炎性小体诱导的焦亡对不同肿瘤的影响具有特异性。在某些肿瘤,如胃癌、结直肠癌和肺癌中,焦亡诱导的细胞炎性反应促进了肿瘤的发展;而在另一些肿瘤中,如肝细胞癌和部分直肠癌中,焦亡诱导的细胞炎性反应则抑制了肿瘤的发展。由于在肿瘤中表现出了"双刃剑"的作用,NLRP3炎性小体诱导的焦亡受到了广泛关注。全文就焦亡的机制和途径,以及NLRP3炎性小体介导的焦亡在肿瘤中的作用作一综述。

Programmed cell death refers to the spontaneous cell death through the mode of gene coding,including apoptosis, pyroptosis, autophagy, necroptosis(also known as programmed necrosis), while pyroptosis is newly found recently. Different from apoptosis, pyroptosis induces the formation of membrane pores on the cell membrane, which leads to the occurrence of extracellular inflammatory reactions. So far, four pathways inducing pyroptosis have been found. The activation of pyroptosis needs to be mediated by multiple cytokines, and inflammasomes are necessary for most pyroptosis-activated pathways. Inflammasomes are polymeric protein complexes, including NOD-like receptor protein 3(NLRP3) inflammasome, which is one of the hotspots in this field because of its ability to mediate pyroptosis in different types of tumors. Researchers have found that NLRP3 inflammasome plays different roles in different tumors. In some tumors, such as gastric cancer, colorectal cancer and lung cancer, pyroptosis induces the reaction of inflammatory to promote the progress of tumor cells;while in others, like hepatocellular cancer and some colorectal cancers, it inhibits the development of tumor. NLRP3 imflammasome-induced pyroptosis has attracted much attention due to its “double-edged sword” role in tumors. In this paper, the mechanism and pathway of pyroptosis, as well as the role of NLRP3 inflammasome-mediated pyroptosis in tumors are discussed.