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细胞焦亡:揭示机制与癌症的关联。

Pyroptosis: shedding light on the mechanisms and links with cancers.

机构信息

Department of Pharmacy, Hangzhou Women's Hospital, Hangzhou, China.

Department of Pharmacy, Shangyu People's Hospital of Shaoxing, Shaoxing, China.

出版信息

Front Immunol. 2023 Nov 2;14:1290885. doi: 10.3389/fimmu.2023.1290885. eCollection 2023.

DOI:10.3389/fimmu.2023.1290885
PMID:38016064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10651733/
Abstract

Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by cell swelling, cytomembrane perforation and lysis, chromatin DNA fragmentation, and the release of intracellular proinflammatory contents, such as Interleukin (IL) 8, IL-1β, ATP, IL-1α, and high mobility group box 1 (HMGB1). Our understanding of pyroptosis has increased over time with an increase in research on the subject: gasdermin-mediated lytic PCD usually, but not always, requires cleavage by caspases. Moreover, new evidence suggests that pyroptosis induction in tumor cells results in a strong inflammatory response and significant cancer regression, which has stimulated great interest among scientists for its potential application in clinical cancer therapy. It's worth noting that the side effects of chemotherapy and radiotherapy can be triggered by pyroptosis. Thus, the intelligent use of pyroptosis, the double-edged sword for tumors, will enable us to understand the genesis and development of cancers and provide potential methods to develop novel anticancer drugs based on pyroptosis. Hence, in this review, we systematically summarize the molecular mechanisms of pyroptosis and provide the latest available evidence supporting the antitumor properties of pyroptosis, and provide a summary of the various antitumor medicines targeting pyroptosis signaling pathways.

摘要

细胞焦亡,是继细胞凋亡和细胞坏死之后发现的一种新型程序性细胞死亡方式,其特征为细胞肿胀、细胞膜穿孔和裂解、染色质 DNA 片段化以及细胞内炎症原性内容物(如白细胞介素 (IL) 8、IL-1β、ATP、IL-1α 和高迁移率族蛋白 B1 (HMGB1))的释放。随着对该主题研究的增加,我们对细胞焦亡的认识也在不断提高:gasdermin 介导的裂解性细胞焦亡通常需要,但并非总是需要半胱天冬酶的切割。此外,新的证据表明,肿瘤细胞中细胞焦亡的诱导会导致强烈的炎症反应和显著的癌症消退,这激发了科学家们对其在临床癌症治疗中应用的极大兴趣。值得注意的是,细胞焦亡会引发化疗和放疗的副作用。因此,智能利用细胞焦亡这把双刃剑,将使我们能够了解癌症的发生和发展,并为基于细胞焦亡的新型抗癌药物的开发提供潜在方法。因此,在这篇综述中,我们系统地总结了细胞焦亡的分子机制,并提供了支持细胞焦亡抗肿瘤特性的最新可用证据,并对靶向细胞焦亡信号通路的各种抗肿瘤药物进行了总结。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/10651733/618fc215b159/fimmu-14-1290885-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/10651733/f9dd4b56710e/fimmu-14-1290885-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/10651733/618fc215b159/fimmu-14-1290885-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/10651733/f9dd4b56710e/fimmu-14-1290885-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9456/10651733/618fc215b159/fimmu-14-1290885-g002.jpg

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Adv Mater. 2023 Nov;35(44):e2305073. doi: 10.1002/adma.202305073. Epub 2023 Sep 21.
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Chemotherapeutic drugs-induced pyroptosis mediated by gasdermin E promotes the progression and chemoresistance of pancreatic cancer.化疗法药物诱导的 GSDME 介导的细胞焦亡促进胰腺癌的进展和化疗耐药性。
Cancer Lett. 2023 Jun 28;564:216206. doi: 10.1016/j.canlet.2023.216206. Epub 2023 Apr 28.
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Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer.
BMC Biol. 2025 Jun 6;23(1):158. doi: 10.1186/s12915-025-02268-x.
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The role and intrinsic connection of cellular senescence and cell death in inflammatory bowel disease.细胞衰老和细胞死亡在炎症性肠病中的作用及内在联系。
Front Cell Dev Biol. 2025 Apr 24;13:1502531. doi: 10.3389/fcell.2025.1502531. eCollection 2025.
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From Inflammasomes to Pyroptosis: Molecular Mechanisms in Chronic Intestinal Diseases - Opportunity or Challenge?从炎性小体到细胞焦亡:慢性肠道疾病中的分子机制——机遇还是挑战?
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