5-ALA mediated PDT induces pyroptosis in colorectal cancer cells by targeting the caspase-1/GSDMD pathway.

IF 2.4 4区医学 Q3 ENGINEERING, BIOMEDICAL

Lasers in Medical Science Pub Date : 2025-08-27 DOI:10.1007/s10103-025-04595-5

Ding-Yuan Zhang, Zeqing Gu, Luyao Shi, Zhongshi Li, Xiaoxue Du, Yanjing Li

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引用次数: 0

Abstract

Photodynamic therapy (PDT) is a minimally invasive treatment modality based on photochemical reactions that damage specific tumour tissues. Pyroptosis is a type of programmed death that relies on the activation of cysteine-containing aspartate proteolytic enzymes (caspases) and cleavage of the gasdermin protein family members. However, the mechanism of 5-aminolevulinic acid (5-ALA)-mediated PDT-induced pyroptosis in colorectal cancer is not well understood. Here, we found that 5-ALA-mediated PDT can induce pyroptosis in colorectal cancer cells, characterized by the appearance of pyroptotic bubbles and the detection of the release of cellular contents and inflammatory factors. Mechanistically, PDT activates caspase-1 and cleaves gasdermin D (GSDMD), and the release of N-GSDMD triggers pyroptosis in colorectal cancer cells. In addition, inhibition of this pathway in vivo can attenuate the therapeutic effect of PDT. In summary, we investigated the role of GSDMD in PDT-mediated pyroptosis in CRC cells, and the results showed that 5-ALA-mediated PDT induces pyroptosis in colorectal cancer cells by targeting the caspase-1/GSDMD pathway. This study may provide a reference for the clinical application of PDT in CRC treatment.

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5-ALA介导的PDT通过靶向caspase-1/GSDMD通路诱导结直肠癌细胞焦亡。

光动力疗法（PDT）是一种基于损伤特定肿瘤组织的光化学反应的微创治疗方式。焦亡是一种程序性死亡，依赖于含半胱氨酸的天冬氨酸蛋白水解酶（半胱天冬酶）的激活和gasdermin蛋白家族成员的裂解。然而，5-氨基乙酰丙酸（5-ALA）介导的pdt诱导结直肠癌焦亡的机制尚不清楚。在这里，我们发现5- ala介导的PDT可以诱导结直肠癌细胞焦亡，其特征是焦亡气泡的出现，并检测到细胞内容物和炎症因子的释放。在机制上，PDT激活caspase-1和裂解气皮蛋白D (GSDMD)， N-GSDMD的释放引发结直肠癌细胞的焦亡。此外，在体内抑制这一途径会减弱PDT的治疗效果。综上所述，我们研究了GSDMD在PDT介导的结直肠癌细胞焦亡中的作用，结果表明5- ala介导的PDT通过靶向caspase-1/GSDMD通路诱导结直肠癌细胞焦亡。本研究可为PDT在结直肠癌治疗中的临床应用提供参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lasers in Medical Science 医学-工程：生物医学

CiteScore

4.50

自引率

4.80%

发文量

192

审稿时长

3-8 weeks

期刊介绍： Lasers in Medical Science (LIMS) has established itself as the leading international journal in the rapidly expanding field of medical and dental applications of lasers and light. It provides a forum for the publication of papers on the technical, experimental, and clinical aspects of the use of medical lasers, including lasers in surgery, endoscopy, angioplasty, hyperthermia of tumors, and photodynamic therapy. In addition to medical laser applications, LIMS presents high-quality manuscripts on a wide range of dental topics, including aesthetic dentistry, endodontics, orthodontics, and prosthodontics. The journal publishes articles on the medical and dental applications of novel laser technologies, light delivery systems, sensors to monitor laser effects, basic laser-tissue interactions, and the modeling of laser-tissue interactions. Beyond laser applications, LIMS features articles relating to the use of non-laser light-tissue interactions.