Xiaozhen Fang alleviates erlotinib-induced skin toxicity in mice by in-hibiting pyroptosis via NLRP3/caspase-1/GSDMD signaling pathway
10.3969/j.issn.1000-4718.2025.07.016
- VernacularTitle:消疹方通过NLRP3/caspase-1/GSDMD信号通路抑制细胞焦亡而减轻EGFR抑制剂所致小鼠皮肤毒性
- Author:
Xintian WANG
1
;
Cheng CHENG
;
Ling LUO
;
Yan CHEN
;
Yuping LIU
;
Haiyan XING
Author Information
1. 南京中医药大学附属中西医结合医院,江苏 南京 210028;南京中医药大学附属中西医结合医院肿瘤科,江苏 南京 210028
- Publication Type:Journal Article
- Keywords:
Xiaozhen Fang;
erlotinib;
skin toxicity;
pyroptosis;
NLRP3/caspase-1/GSDMD signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(7):1392-1399
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.
