新医学2026，Vol.57Issue(2)：129-138,10.DOI:10.12464/j.issn.0253-9802.2025-0309
阴阳攻积丸通过caspase3/GSDME通路诱导肝癌细胞焦亡的作用研究
Study on the mechanism of YinYang Gongji Pill in inducing pyroptosis of hepatoma carcinoma cells via the caspase-3/GSDME pathway
摘要
Abstract
Objective To investigate the mechanism by which YinYang Gongji Pill(YYGJ)induces pyroptosis in hepatocellular carcinoma cells.Methods Network pharmacology was employed to analyze the potential targets and mechanisms of YYGJ in the treatment of hepatocellular carcinoma.Molecular docking was performed between the main active components of YYGJ and key target caspase-3.Human hepatocellular carcinoma Huh7 cells were treated with different concentrations of YYGJ,and cell viability was measured using the CCK-8 assay to determine the optimal drug concentration.Huh7 cells were divided into the blank control,low-,medium-,and high-dose YYGJ,and positive control(oxaliplatin)groups.Wound healing and Transwell assays were used to evaluate cell migration and invasion capabilities,respectively.Cytotoxicity was assessed by LDH release assay.The expression levels of IL-18 and IL-1β in the cell supernatant were measured using ELISA.The expression levels of pyroptosis-related proteins(caspase-3,cleaved caspase-3,gasdermin E(GSDME)and GSDME-N)were detected by Western blot.Results Network pharmacology identified the top five active components of YYGJ including berberine,tangeretin,tetrahydroberberine,sitosterol,and quercetin,and the key target caspase-3.Molecular docking showed strong binding affinity between these components and caspase-3.GO and KEGG enrichment analyses indicated that the anti-tumor effects of YYGJ were closely associated with inflammation and pyroptosis.Compared with the blank control group,YYGJ significantly inhibited the proliferation,migration,and invasion of Huh7 cells in a concentration-dependent manner(all P＜0.05).Additionally,YYGJ treatment markedly increased LDH release,elevated IL-18 and IL-1β levels,and up-regulated the expression levels of cleaved caspase-3 and GSDME-N proteins(all P＜0.05).Conclusion YYGJ may induce pyroptosis in hepatocellular carcinoma cells via the caspase-3/GSDME pathway,thereby suppressing malignant progression of hepatocellular carcinoma.关键词
阴阳攻积丸/肝细胞癌/细胞焦亡/网络药理学/分子对接Key words
YinYang Gongji Pill/Hepatocellular carcinoma/Pyroptosis/Network pharmacology/Molecular docking引用本文复制引用
陈然,谢和平,李永伟..阴阳攻积丸通过caspase3/GSDME通路诱导肝癌细胞焦亡的作用研究[J].新医学,2026,57(2):129-138,10.基金项目
广东省自然科学基金面上项目(2022A1515011689,2023A1515011937) （2022A1515011689,2023A1515011937）
国家中医药管理局中西医协同"旗舰"科室建设项目(2025TGL0370000014) （2025TGL0370000014）
广东省中医药局资助项目(20251062) （20251062）
