基于网络药理学探讨肝积方治疗肝细胞癌作用机制  

Discussion on Therapeutic Mechanism of Ganji Prescription on Hepatocellular Carcinoma Based on Network Pharmacology

作　　者：王珏 张春蕾 杨铭[3] 杨悦 郑培永 宋海燕 WANG Jue;ZHANG Chunlei;YANG Ming;YANG Yue;ZHENG Peiyong;SONG Haiyan(Institute of Digestive Diseases,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Office of National Drug Clinical Trial,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院脾胃病研究所,上海200032 [2]上海中医药大学附属龙华医院,上海200032 [3]上海中医药大学附属龙华医院国家药物临床试验机构办公室,上海200032

出　　处：《中国中医药信息杂志》2023年第1期32-38,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：上海市自然科学基金(20ZR1458900);上海市青年科技英才扬帆计划项目(20YF1450000)。

摘　　要：目的采用网络药理学方法分析肝积方对肝细胞癌(HCC)的可能作用靶点和相关机制,并进行体内实验验证。方法采用TCMSP、HIT、TCMID、STITCH数据库查找肝积方主要化学成分及作用靶点,收集GeneCards数据库中与HCC相关基因,建立疾病-靶点-化学成分网络。通过GO和KEGG通路富集分析肝积方对肝癌可能的作用途径。建立肝纤维化背景的SD大鼠原位HCC模型,并予肝积方灌胃干预,检测大鼠原位瘤大小并称重,应用Western blot检测瘤组织相关信号通路蛋白表达。结果通过数据库检索共获得肝积方有效成分127个,主要成分对HCC的作用靶点共301个。KEGG富集分析获得肝积方与HCC显著共关联的信号通路,包括PI3K-AKT、TNF-α、IL-17等信号通路。动物实验显示,肝积方显著减轻大鼠HCC体积和瘤重,下调瘤组织AKT活化水平,并逆转HCC上皮间质转化(EMT)相关分子的表达水平。结论肝积方对HCC有明显抑制作用,调控PI3K-AKT信号通路抑制HCC细胞EMT可能是其部分作用机制。Objective To explore the potential therapeutic target and mechanism of Ganji Prescription in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and further verification via in vivo experiments.Methods Effective chemicals and targets of Ganji Prescription were searched in TCMSP,HIT,TCMID,and STITCH databases.A disease-target-chemical network was established using HCC-associated genes screened through the GeneCards database.The possible functional approaches of Ganji Prescription on HCC were predicted by the enriched analysis of GO and KEGG pathways.An orthotopic HCC model in SD rats with liver fibrosis background was established,and the Ganji Prescription was administered orally for intervention.The size of the orthotopic tumor in the rat was detected and weighed.Western blot was used to detect changes in protein expression associated with the predicted signaling pathways in tumor tissues.Results A total of 127 effective compounds and 301 main targets of Ganji Prescription were screened through database retrieval.KEGG enrichment analysis obtained significant co-associated signaling pathways between Ganji Prescription and HCC,including PI3K-AKT,TNF-αand IL-17 signaling pathways,et.al.Animal experiments showed that Ganji Prescription significantly reduced HCC volume and tumor weight in rats,down-regulated the activation level of AKT in tumor tissue,and reversed the expression levels of HCC epithelial-mesenchymal transition(EMT)-related molecules.Conclusion Ganji Prescription has obvious inhibitory effect on HCC,and regulating PI3K-AKT signaling pathway to inhibit EMT of HCC cells may be part of its mechanism of action.

关 键 词：网络药理学 肝细胞癌 肝积方 PI3K-AKT信号通路 上皮间质转化 

分 类 号：R283.5[医药卫生—中药学] R273.57[医药卫生—中医学]