医药导报2026，Vol.45Issue(8)：1315-1324,10.DOI:10.3870/j.issn.1004-0781.2026.08.002
7-氟-4-(4-氯苯氧基)喹啉化合物对肺癌A549细胞焦亡研究
Study on the Pyroptosis of Lung Cancer A549 Cells Induced by 7-Fluoro-4-(4-chlorophenoxy)Quinoline Compound
摘要
Abstract
Objective To explore 7-Fluoro-4-(4-chlorophenoxy)(IB)molecular mechanisms of inducing pyroptosis in lung cancer A549 cells.Methods The potential targets of IB were screened by bioinformatics,and the"drug-target-pathway"network was constructed,and its binding ability to cysteine-aspartate-specific proteolytic enzymes(caspase)-1 and caspase-3 was analysed by molecular docking.The spheroid model of A549 was established by three-dimensional culture of coating solution,and the induction of pyroptosis of IB and its mechanism were verified by acid phosphatase assay,enzyme-linked immunosorbent assay,western blotting assay and cell thermal displacement assay.Results A total of 23 intersecting targets(caspase-1,caspase-3,epidermal growth factor receptor,etc.)were screened,and Kyoto Encyclopedia of Genes and Genomes(KEGG)Enrichment Analysis showed that nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome was significantly regulated.IB binds to caspase-1 and caspase-3 with high affinity;IB inhibited cell proliferation in a dose-dependent manner,upregulated interleukin-1β(IL-1β)secretion,activated NOD-like receptor pyrotin domain-associated protein 3(NLRP3)/caspase-1/caspase-3,and promoted gasdermin D(GSDMD)/gasdermin E(GSDME)cleavage.Cellular thermal displacement assays confirmed that 7-fluoro-4-(4-chlorophenoxy)quinoline directly binds to caspase-1/3,and disulfiram reverses the pyroptosis phenotype.Conclusion 7-Fluoro-4-(4-chlorophenoxy)quinoline co-induces pyroptosis in A549 cells through the NLRP3/caspase-1/GSDMD classical pathway and caspase-3/GSDME non-canonical pathway,providing a new strategy for the treatment of non-small cell lung cancer.关键词
三维细胞培养模型/喹啉化合物/肿瘤细胞焦亡/生物信息学Key words
Three-dimensional cell culture model/Quinoline compound/Pyroptosis of tumor cells/Bioinformatics分类
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杨金雨,门珊珊,徐东萍,杜诗瑶,刘丹,汪海峰..7-氟-4-(4-氯苯氧基)喹啉化合物对肺癌A549细胞焦亡研究[J].医药导报,2026,45(8):1315-1324,10.基金项目
辽宁省教育厅科学研究经费项目青年科技人才育苗项目(LQ2020021). （LQ2020021）
