黑色素瘤中的细胞焦亡机制及其潜在治疗策略
The Mechanism of Cell Pyroptosis in Melanoma and Potential Therapeutic Strategies
摘要: 焦亡是由Gasdermins蛋白家族介导的程序性细胞死亡，其执行机制依赖于caspase-1或caspase-4/5/11对Gasdermin D (GSDMD)的特异性切割。该切割导致GSDMD的N端成孔结构域(PFD)与C端阻遏结构域(RD)分离，进而形成膜穿孔，最终介导细胞死亡。PFD寡聚化在膜中形成大孔，从而驱动溶胀和膜破裂。细胞焦亡在免疫反应中起着重要作用，但过度激活可能与多种疾病的发生相关，如感染、自身免疫疾病和肿瘤。黑色素瘤的发病率在世界范围内迅速增加，不仅是男性第五大最常见的癌症类型之一，也是女性第六大最常见的癌症类型之一，成为一个严重的公共卫生问题。近年来的研究发现，焦亡在黑色素瘤的发生及发展中发挥着关键作用，靶向促进细胞焦亡的药物在黑色素瘤的治疗中具有巨大潜力。本文讨论了焦亡的概念和调控机制、焦亡在黑色素瘤中的作用及其机制以及靶向黑色素瘤的潜在治疗价值。
Abstract: Pyroptosis is a programmed cell death mediated by the Gasdermins protein family, and its execution mechanism depends on the specific cleavage of Gasdermin D (GSDMD) by caspase-1 or caspase-4/5/11. This cleavage results in the separation of the N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD) of GSDMD, which subsequently forms a membrane perforation and ultimately mediates cell death. PFD oligomerization forms macropores in the membrane, which drives swelling and membrane rupture. Pyroptosis plays an important role in the immune response, but excessive activation may be associated with the occurrence of a variety of diseases, such as infections, autoimmune diseases, and tumors. The incidence of melanoma is rapidly increasing worldwide, becoming not only the fifth most common type of cancer in men but also the sixth most common type of cancer in women, posing a serious public health problem. Recent studies have found that pyroptosis plays a key role in the occurrence and development of melanoma, and drugs targeting pyroptosis have great potential in the treatment of melanoma. This review discusses the concept and regulatory mechanism of pyroptosis, the role and mechanism of pyroptosis in melanoma, and the potential therapeutic value of targeting melanoma.
文章引用：黄晓敏. 黑色素瘤中的细胞焦亡机制及其潜在治疗策略[J]. 临床医学进展, 2026, 16(3): 90-98. https://doi.org/10.12677/acm.2026.163766

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