细胞焦亡在胃癌中的作用及中医药调控研究进展

Regulation of Pyroptosis in Gastric Cancer by Traditional Chinese Medicine:A Review

细胞焦亡是区别于细胞凋亡、坏死、细胞增多症、铁死亡和自噬的一种新型炎性胱天蛋白酶(Caspase)依赖性程序性细胞死亡。细胞焦亡依赖于Caspase蛋白家族的激活,切割关键介质蛋白使细胞膜形成孔隙,诱导促炎细胞因子白细胞介素-1β和白细胞介素-18成熟并释放到细胞外环境中,产生级联炎症反应。胃癌是一种恶性的消化道肿瘤疾病,具有难治愈、预后差、放化疗并发症多等特点。目前胃癌的发病机制尚不明确,越来越多的研究发现,细胞焦亡与胃癌发生发展关系密切,这种新型的死亡方式被广泛关注。细胞焦亡对于胃癌而言是一把双刃剑,一方面可以释放促炎细胞内容物来放大或维持炎症,诱导细胞的“炎-癌”转化;另一方面细胞焦亡可以增强化疗药物的敏感性,增强治疗效果,提高胃癌生存率。近年来,中医药抗肿瘤作用机制的研究成为研究热点,并在临床应用中疗效显著,因此,以中医药调节细胞焦亡作为切入点可能是未来治疗胃癌的新方向。基于上述研究,该文总结了细胞焦亡关键蛋白与胃癌发生、发展的作用机制,归纳了中药复方及中药活性成分通过介导细胞焦亡通路,减轻胃黏膜损害,降低胃癌发生率,以及预防肿瘤转移与复发的作用,以期为今后探索细胞焦亡机制和中医药治疗胃癌提供新思路。

Pyroptosis,a new type of inflammatory programmed cell death,is different from apoptosis,necrosis,cytosis,ferroptosis,and autophagy.Pyroptosis is dependent on the activation of cysteine aspartate-specific protease(Caspase),which cleaves key mediator proteins to form pores in the cell membrane and induces the maturation and release of the proinflammatory cytokines interleukin-1βand interleukin-18 into the extracellular environment,resulting in a cascade of inflammatory reactions.Gastric cancer as a malignant tumor of the digestive tract is refractory and has poor prognosis,and the chemoradiotherapy of this disease may lead to a variety of complications.At present,the pathogenesis of gastric cancer remains unclear.Studies have proved that pyroptosis is associated with the occurrence and development of gastric cancer,which has attracted wide attention.Pyroptosis is a double-edged sword for gastric cancer.On the one hand,it can release the contents of proinflammatory cells to amplify or maintain inflammation and induce the"inflammation-cancer"transformation of cells.On the other hand,pyroptosis can enhance the sensitivity of drugs for chemotherapy to improve the therapeutic effect and survival.In recent years,the anti-tumor mechanism of traditional Chinese medicine(TCM)has become a research hotspot as TCM has demonstrated significant effects in clinical application.Therefore,the regulation of pyroptosis by TCM may be a new direction for the treatment of gastric cancer in the future.Based on the available studies,this paper introduces the roles of pyroptosis-associated key proteins in the occurrence and development of gastric cancer.Furthermore,this paper summarizes the effects of TCM prescriptions and active ingredients on alleviating gastric mucosal damage,reducing the incidence of gastric cancer,and preventing tumor metastasis and recurrence by mediating pyroptosis pathways,aiming to provide new ideas for deciphering the mechanism of pyroptosis and exploring the TCM treatment of gastric cancer in the future.