基于网络药理学及分子对接探讨半枝莲半边莲药对治疗肺癌的作用机制  

Exploring the Mechanismof Scutellaria Barbata-Lonelia in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking

作　　者：庞雪莹 赵欣华 韩笑[1] 张俐佳 刘业 王业伟[2] PANG Xueying;ZHAO Xinhua;HAN Xiao;ZHANG Lijia;LIU Ye;WANG Yewei(The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;The Cancer Hospital of Harbin Medical University,Harbin 150080,China)

机构地区：[1]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [2]哈尔滨医科大学附属肿瘤医院,黑龙江哈尔滨150080

出　　处：《特产研究》2024年第3期30-41,46,共13页Special Wild Economic Animal and Plant Research

基　　金：中国博士后科学基金“地区专项支持计划”项目(2002MD713752);黑龙江省中医药管理局项目(ZHY2020-099、ZHY18-059)。

摘　　要：本研究旨在运用网络药理学、分子对接及动物试验,探寻半枝莲-半边莲药对治疗肺癌的作用机制。本研究运用TCMSP平台查询半枝莲-半边莲药对的化合物成分,使用Cytoscape3.7.2软件绘制成分-靶点网络图。利用GeneCards和OMIM数据库查询肺癌靶点,通过相互作用数据库平台STRING进行靶蛋白互作分析。构建核心活性成分、核心靶点与关键通路相互作用关系图,并对核心活性成分与靶点进行分子对接。雄性SD大鼠随机分为空白组、模型组、中药组(6.3g/kg),每组6只,采用气管内灌注致癌碘化油溶液法建立肺癌大鼠模型,并采用病理学检查验证造模是否成功;采用Western blot检测肿瘤组织中p-PI3K,p-Akt,EGFR和IL-6蛋白的表达情况。结果分析显示,有效活性成分及其对应靶点分别为44个、108个,主要有效活性成分为Quercetin,Kaempferol,Luteolin,Wogonin,Baicalein等。共筛选出肺癌靶点2 057个,Venny图显示二者交集靶点74个。PPI网络分析度值较高的靶蛋白为IL-6,EGFR,CASP3,ESR1,MYC,VEGFA,CCND1,MAPK8。GO分析显示,富集于多个生物过程、分子功能及细胞组分。KEGG信号通路分析显示主要富集在TNF信号通路,PI3K-Akt信号通路,p53信号通路等通路。成分-靶点-通路网络图显示,半枝莲-半边莲药对可能由Quercetin,Kaempferol,Luteolin,Wogonin,Baicalein等活性成分组成,通过作用于IL-6,EGFR,CCND1,MYC,VEGFA,MAPK8等靶蛋白,调节PI3K-AKT信号通路,MAPK信号通路等来发挥治疗肺癌作用。分子对接结果显示,IL-6与槲皮素,EGFR、MYC、CCND1与汉黄芩素有良好的结合能力。Western blot结果表明,相较于模型组,中药组中大鼠瘤组织中p-PI3K、p-Akt、EGFR和IL-6蛋白表达均明显下降(P <0.05)。半枝莲-半边莲药对对肺癌的治疗作用是通过多种活性成分,多个靶点,多途径来实现的,本研究为今后进行深入的机制研究提供了理论依据。Exploring the Mechanism of Action of Scutellaria barbata-Lobelia in treating lung cancer through network pharmacology,mol-ecular docking,and animal experiments.The TCMSP platform was used to query the compounds of Scutellaria barbata-Lobelia pairs,and Cytoscape 3.7.2 software was used to draw the component-target network diagrams.GeneCards and OMIM databases were used to query the lung cancer targets,and STRING,the interaction database platform,was used to analyze the interactions between target proteins.Con-struct a diagram of the interaction between core active ingredients,core targets,and key pathways,and perform molecular docking between core active ingredients and targets.Male SD rats were randomly divided into a blank group,a model group,and a traditional Chinese medi-cine group(6.3g/kg),with 6 rats in each group.A lung cancer rat model was established by intratracheal infusion of carcinogenic iodized oil solution.Pathological examination to verify whether the modeling was successful;western blot was used to detect the expression of p-PI3K,p-Akt,EGFR,and IL-6 proteins in tumor tissue.Analysis shows that there are 44 active ingredients and 108 corresponding targets,respectively,and the main effective active ingredients were quercetin,kaempferol,luteolin,wogonin,baicalein and so on.A total of 2,057 lung cancer targets were identified,and the Venny diagram showed 74 intersecting targets.The target proteins with higher values in PPI net-work,which were IL-6,EGFR,CASP3,ESR1,MYC,VEGFA,CCND1,MAPK8.GO analysis showed that it is mainly enriched in multiple biological processes,molecular functions,and cellular components.The analysis of KEGG signaling pathway showed that it was mainly en-riched in TNF signaling pathway,PI3K-Akt signaling pathway,p53 signaling pathway and other pathways.The component-target-pathway network diagram shows that the pairs may be composed of quercetin,kaempferol,luteolin,wogonin,baicalein,etc.,which exert their therapeutic effects by acting on target proteins,such as IL-6,EGFR,CCND1,MYC,VE

关 键 词：网络药理学 半枝莲-半边莲 肺癌 PI3K-AKT信号通路 

分 类 号：R285[医药卫生—中药学]