文献类型：期刊文献

中文题名：基于网络药理学和动物实验探讨桔梗白散治疗肺腺癌作用机制

英文题名：Exploration on the Mechanism of Jiegengbai Powder in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology and Animal Experiments

作者：袁超[1];姜佳辰[1];孔思琪[1];梁建庆[1];张毅[1];张悦[1];刘瑜[1];李金田[1]

第一作者：袁超

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：31

期号：9

起止页码：33

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(82160872);甘肃省教育厅“双一流”科研重点项目(GSSYLXM-05);甘肃省中医药研究中心开放课题(zyzx-2020-zx17);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金(2022-13);甘肃中医药大学研究生创新基金项目(2023年)。

语种：中文

中文关键词：桔梗白散;顺铂;化疗;肺腺癌;网络药理学;PTEN;PI3K/Akt/mTOR信号通路

外文关键词：Jiegengbai Powder;cisplatin;chemotherapy;lung adenocarcinoma;network pharmacology;PTEN;PI3K/Akt/mTOR signaling pathway

摘要：目的 基于网络药理学方法和动物实验探讨桔梗白散治疗肺腺癌的作用靶点及机制。方法 借助TCMSP数据库及GeneCards、PharmGKB、DrugBank、TTD、OMIM数据库检索桔梗白散有效成分相关靶点及肺腺癌相关靶点,获取二者交集靶点,运用Cytoscape3.8.0软件构建交集靶点蛋白相互作用(PPI)网络和中药活性成分-靶点网络,筛选关键成分及核心靶点。对交集靶点进行GO和KEGG富集分析。运用PyMOL、AutoDockTools1.5.6软件对关键成分与核心靶点进行分子对接。建立肺癌小鼠模型,将小鼠随机分为空白组、模型组、顺铂组、桔梗白散联合顺铂组及桔梗白散低、中、高剂量组,给药组分别予相应药物干预14 d,计算抑瘤率,HE染色观察肿瘤组织形态,RT-qPCR及Western blot检测肿瘤组织PI3K、PTEN、Akt、mTOR基因及蛋白表达。结果 网络药理学方法筛选出桔梗白散治疗肺腺癌的TP53、CASP3、BCL2L1、AKT1等核心靶点,富集的关键通路有PI3K-Akt信号通路等。桔梗白散能有效抑制模型小鼠肿瘤生长;与模型组比较,桔梗白散中、高剂量组PI3K、Akt、mTOR mRNA表达降低,PTEN mRNA表达升高,p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR比值降低,PTEN蛋白表达升高(P<0.05,P<0.01)。结论 桔梗白散治疗肺腺癌具有多层次、多靶点的特点,可能通过调控PI3K/Akt/mTOR信号通路促进肿瘤细胞凋亡与自噬,从而发挥抑制肿瘤细胞生长的作用。
Objective To explore the targets and mechanism of Jiegengbai Powder in the treatment of lung adenocarcinoma based on network pharmacology and animal experiments.Methods The targets of effective components of Jiegengbai Powder were obtained from TCMSP,the targets of lung adenocarcinoma were screened from GeneCards,PharmGKB,DrugBank,TTD,OMIM databases,and the intersection targets were obtained.The protein-protein interaction(PPI)network and active components of Chinese materia medica-target network were constructed by using Cytoscape 3.8.0 software,and the key components and core targets were screened out.The intersection targets were analyzed by GO and KEGG enrichment analysis.PyMOL and AutoDockTools 1.5.6 software were used to verify the molecular docking between the key components and core targets.The lung cancer mice model was established.The mice were randomly divided into blank group,model group,cisplatin group,Jiegengbai Powder combined with cisplatin group,Jiegengbai Powder low-,medium-and high-dosage groups.After 14 days of intervention,the tumor inhibition rate was calculated,and the morphology of tumor tissues was observed by HE staining.The gene and protein expressions of PI3K,PTEN,Akt and mTOR in tumor tissues were detected by RT-qPCR and Western blot.Results The core targets of Jiegengbai Powder in the treatment of lung adenocarcinoma such as TP53,CASP3,BCL2L1 and AKT1 were screened by network pharmacology.The key pathways of enrichment were PI3K-Akt signaling pathway and so on.Jiegengbai Powder can inhibit the growth of tumor effectively.Compared with the model group,the mRNA expressions of PI3K,Akt and mTOR decreased in the Jiegengbai Powder medium-and high-dosage groups,and PTEN mRNA expression increased,the ratio of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR decreased,and the expression of PTEN protein increased(P<0.05,P<0.01).Conclusion Jiegengbai Powder has the characteristics of multi-level and multi-target in the treatment of lung adenocarcinoma.It may promote tumor cell apoptosis and autophagy by regulating PI3K/Akt/mTOR signaling pathway,so as to achieve the anti-tumor effect of inhibiting tumor cell growth.