基于网络药理学及细胞实验探析乌附理中汤治疗胃癌的作用机制  

Exploration into the Mechanism of Wufu Lizhong Tang in the Treatment of Gastric Cancer Based on Network Pharmacology and Cellular Experiment

作　　者：马祺 杨斌锋 乔玉洁 黄邦荣[1] MA Qi;YANG Binfeng;QIAO Yujie;HUANG Bangrong(Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,China)

机构地区：[1]甘肃省中医院,甘肃兰州730050

出　　处：《西部中医药》2025年第4期33-41,共9页Western Journal of Traditional Chinese Medicine

基　　金：甘肃省自然科学基金(21JR1RA054);甘肃省科技计划项目(18JR2FA001);省级区域中医(专项)诊疗项目--肿瘤多学科诊疗中心。

摘　　要：目的:利用网络药理学和细胞实验探究乌附理中汤治疗胃癌的作用机制。方法:通过网络药理学预测乌附理中汤的有效成分,核心靶点和信号通路,选用胃癌细胞HGC27细胞、MKN28细胞通过CCK-8实验、RT-qPCR实验、Western blot实验、细胞划痕实验验证网络药理学预测的主要靶点以探究乌附理中汤治疗胃癌的作用机制。结果:乌附理中汤共含活性成分198个,对应靶点884个;从GEO数据库中共检索到胃癌相关差异基因919个,获取交集靶点61个,其中MMP9、OLR1、PTGS2、MMP12、IL-6、SELE、MMP7、NOX4等为核心靶点;富集分析显示交集靶点主要富集在PI3K/AKT、AGE-RAGE、TNF、cAMP、NF-kappa B、IL-17、cGMP-PKG等信号通路。CCK-8、划痕实验提示,乌附理中汤能明显抑制HGC27细胞和MKN28细胞的增殖、迁移及侵袭能力(P<0.05)。RT-qPCR实验结果表明,乌附理中汤能降低SLUG、MMP9、Vimentin、VEGF mRNA表达水平(P<0.05)。Western blot实验结果表明乌理中汤能降低p-AKT、SLUG、MMP9、Vimentin、VEGF蛋白表达水平(P<0.05)。结论:乌附理中汤通过抑制AKT/GSK-3β/Snail(Slug)信号通路达到抑制胃癌的目的。Objective:To discuss the mechanism of Wufu Lizhong Tang in the treatment of gastric cancer using network pharmacology and cellular experiment.Methods:The active ingredients,core targets and signaling pathways of the decoction were predicted via network pharmacology,gastric cancer cells HGC27 cells,MKN28 cells were applied to verify the main targets predicted by network pharmacology via CCK-8 experiment,RT-qPCR experiment,Western blot experiment and cellular scratch wound assay,so as to survey the mechanism of Wufu Lizhong Tang in the treatment of gastric cancer.Results:The decoction contained 198 active ingredients and 884 corresponding targets;A total of 919 differential genes associated with gastric cancer were retrieved from GEO database,and 61 intersecting targets were obtained,among them,MMP9,OLR1,PTGS2,MMP12,IL-6,SELE,MMP7 and NOX4 were the core targets;Enrichment analysis revealed that the intersecting targets were mainly enriched in PI3K/AKT,AGE-RAGE,TNF,cAMP,NF-kappa B,IL-17 and cGMP-PKG.CCK-8 and cellular scratch wound assay suggested that the decoction could obviously restrain the proliferation,migration and invasion of HGC27 cells and MKN28 cells(P<0.05).The results of RT-qPCR experiment demonstrated that the decoction could lower the expressions of SLUG,MMP9,Vimentin and VEGF mRNA(P<0.05).The results of Western blot experiment showed that the decoction could reduce the levels of p-AKT,SLUG,MMP9,Vimentin and VEGF protein(P<0.05).Conclusion:Wufu Lizhong Tang could inhibit gastric cancer through restraining AKT/GSK-3β/Snail(Slug)signaling pathway.

关 键 词：胃癌 乌附理中汤 网络药理学 AKT/GSK-3β/Snail(Slug)信号通路 

分 类 号：R285[医药卫生—中药学]