基于网络药理学和血清药理学探讨海牡方治疗非小细胞肺癌的作用机制  

Exploring the Mechanism of Haimufang Decoction in the Treatment of Non-small Cell Lung Cancer Based on Network Pharmacology and Serum Pharmacology

作　　者：马伟平 李昕 刘明[2,3] 刘红兵 MA Weiping;LI Xin;LIU Ming;LIU Hongbing(Department of Pharmacy,Tianjin First Central Hospital,Tianjin 300000,China;Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory of Marine Drugs and Biological Products of Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China;NMPA Key Laboratory for Quality Research and Evaluation of Marine Traditional Chinese Medicine,Qingdao 266000,China)

机构地区：[1]天津市第一中心医院药学部,天津300000 [2]中国海洋大学医药学院,海洋药物教育部重点实验室,山东青岛266003 [3]青岛海洋科学与技术国家实验室,海洋药物与生物制品功能实验室,山东青岛266237 [4]国家药品监督管理局海洋中药质量研究与评价重点实验室,山东青岛266000

出　　处：《中国现代应用药学》2024年第13期1781-1789,共9页Chinese Journal of Modern Applied Pharmacy

基　　金：青岛海洋科学与技术试点国家实验室重大科技专项(2018SDKJ0405-01);中央引导地方科技发展资金(黄河流域协同科技创新)项目(YDZX2023014)。

摘　　要：目的 通过运用网络药理学和血清药理学方法探讨海牡方(Haimufang Decoction,HMF)治疗非小细胞肺癌(nonsmall cell lung cancer,NSCLC)的主要成分、核心靶点、关键信号通路以阐明其可能的作用机制。方法 分别采用TCMSP和DisGeNET等数据库检索、汇总HMF的化合物成分、作用靶点及NSCLC疾病相关靶点;将药物的作用靶点与疾病的靶点取交集获得共有靶点,并上传至STRING数据平台构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络筛选核心靶点;运用DAVID数据库对核心靶点进行GO及KEGG富集分析,并采用Cytoscape 3.9.1软件构建HMF“药味-成分-靶点-通路”网络,预测HMF可能的作用机制;最后通过HMF含药血清对NSCLC NCI-H1975细胞的细胞周期阻滞和细胞凋亡诱导试验验证HMF对肺癌的作用及其潜在机制。结果 从HMF中鉴定了65个化合物,筛选出24-酮胆固醇、槲皮素、邻苯二甲酸二异丁酯等47个主要化合物,PPI网络分析结果显示,肿瘤蛋白p53、肿瘤坏死因子、半胱氨酸天冬氨酸蛋白酶-3等共55个可能是HMF治疗NSCLC的核心靶蛋白,涉及癌症通路等多条信号通路。在随后的验证实验中,癌症通路中的细胞周期阻滞和凋亡诱导已被证实参与抑制NSCLC。结论 HMF通过多成分、多靶点和多途径信号通路的方式发挥治疗NSCLC的作用,为HMF的作用机制和临床应用提供了理论基础。OBJECTIVE To elucidate the possible mechanism,and to explore the main components,core targets,and key signaling pathways of Haimufang Decoction(HMF)in treating non-small cell lung cancer(NSCLC)by the network pharmacology and serum pharmacology methods.METHODS TCMSP and DisGeNET databases were used to search and summarize the components,targets and non-small cell lung cancer-related targets of HMF,respectively.The common targets were obtained by intersection of drug targets and disease targets,and uploaded to the STRING data platform to construct a protein-protein interaction(PPI)network to screen core targets.GO and KEGG enrichment analysis of core targets were performed using DAVID database.Cytoscape 3.9.1 software was used to construct the network of"HMF flavor-components-targets-pathways",predicting the possible mechanisms of action of HMF.Finally,the cell cycle arrest and apoptosis induction experiments of HMF-containing serum on NSCLC NCI-H1975 cells were used to verify the effect of HMF on lung cancer and its potential mechanism.RESULTS A total of 65 compounds were identified from HMF,and 47 main compounds such as 24-keto-cholesterol,quercetin and diisobutyl phthalate were screened out.PPI network analysis shown that tumor protein p53,tumor necrosis factor,cystein-asparate protease-3 and other 55 proteins might be the core target proteins of HMF in the treatment of NSCLC, involving multiple signaling pathways such as pathways in cancer. In subsequent validation experiments, cell cycle arrest and apoptosis induction in the pathways in cancer pathway have been shown to be involved in the inhibition of non-small cell lung cancer. CONCLUSION HMF plays a role in the treatment of NSCLC through multi-component, multi-target and multi-channel signaling pathways, which provides a theoretical basis for the mechanism and clinical application of HMF.

关 键 词：网络药理学 海牡方 含药血清 细胞周期 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]