College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
College of Agriculture and Forestry Science, Linyi University, Linyi, China.
Cell Death Dis. 2019 Sep 9;10(9):650. doi: 10.1038/s41419-019-1883-8.
Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti- and protumor effects of pyroptosis and its potential applications in cancer treatment.
程序性细胞死亡（PCD）是指细胞根据特定基因编码的信号或活性而死亡的方式。细胞凋亡、自噬和细胞焦亡都是 PCD 的机制。在这些机制中，细胞焦亡是由 gasdermin 家族介导的，伴随着炎症和免疫反应。细胞焦亡与癌症之间的关系很复杂，细胞焦亡对癌症的影响因组织和遗传背景而异。一方面，细胞焦亡可以抑制肿瘤的发生和发展；另一方面，作为一种促炎死亡方式，细胞焦亡可以形成适合肿瘤细胞生长的微环境，从而促进肿瘤生长。此外，诱导肿瘤细胞焦亡也被认为是一种潜在的癌症治疗策略。研究表明，DFNA5（非综合征性听力损失蛋白 5）/GSDME（Gasdermin-E）mRNA 甲基化导致大多数肿瘤细胞中 DFNA5/GSDME 的表达水平低于正常细胞，使得大多数肿瘤细胞难以激活细胞焦亡。在恶性肿瘤的治疗中，可以根据 DFNA5/GSDME 的表达水平选择合适的化疗药物，使肿瘤细胞中的 DFNA5/GSDME 上调，从而提高对化疗药物的敏感性，降低耐药性。因此，诱导细胞焦亡可能在癌症治疗中起主要作用。在这里，我们综述了细胞焦亡的抗肿瘤和促肿瘤作用及其在癌症治疗中的潜在应用的最新研究进展。
