학술논문
基于网络药理学和分子对接探索双氢青蒿素治疗口腔鳞状细胞癌的作用机制及实验验证 / Mechanism Research and Experimental Verification of Dihydroartemisinin Used for Treating Oral Squamous cell Carcinoma through Network Pharmacology and Molecular Docking
Document Type
Academic Journal
Source
湖北医药学院学报 / Journal of Hubei University of Medicine. 42(6):612-619
Subject
Language
Chinese
ISSN
1006-9674
Abstract
目的:利用网络药理学及分子对接研究双氢青蒿素治疗口腔鳞状细胞癌的可能机制,并对核心靶点进行实验验证.方法:通过PharmMapper等数据库获得双氢青蒿素的作用靶点,基于GeneCards等数据库获取口腔鳞状细胞癌疾病靶点,取交集靶点即为双氢青蒿素治疗口腔鳞状细胞癌的潜在靶点.利用STRING数据库建立交集靶点蛋白质-蛋白质互作网络,通过CytoScape软件处理数据并筛选核心靶点.利用Metascape数据库进行GO及KEGG富集分析.AutoDock软件对药物、核心靶点进行分子对接.用不同浓度的双氢青蒿素处理口腔鳞状细胞癌CAL-27 细胞,通过CCK-8 检测细胞活力;RT-qPCR检测核心靶点mRNA的表达水平.结果:得到药物治疗疾病靶点148 个,其中核心靶点7 个.GO分析示交集靶点涉及条目共601 条,包括protein kinase activity、protein tyrosine kinase activity等,KEGG富集分析示交集靶点涉及信号通路 167 条,包括 Pathways in cancer、PI3K-Akt signaling pathway等.分子对接提示双氢青蒿素与核心靶点能较好的结合.CCK-8 结果示双氢青蒿素可明显抑制CAL-27细胞的活力,呈浓度依赖性.RT-qPCR结果示,在一定浓度双氢青蒿素作用下,细胞中SRC、PIK3R1、PIK3CA和PTPN11 的mRNA表达量降低.结论:双氢青蒿素可能通过作用于SRC、PIK3R1 等多个靶点,在口腔鳞状细胞癌中发挥抗肿瘤作用.
Objective Network pharmacology and molecular docking were used to study the possible mechanism of dihydro-artemisinin in the treatment of oral squamous cell carcinoma,and the core targets were experimentally verified.Methods The targets of dihydroartemisinin were obtained through PharmMapper and other databases,and GeneCards and other data-bases were used to obtain the disease targets of oral squamous cell carcinoma.The intersection targets were the potential tar-gets of dihydroartemisinin treating oral squamous cell carcinoma.The potential target protein-protein interaction network was established through the STRING database,and the data processed by CytoScape software and screened for core targets.Metascape was used for GO and KEGG enrichment analysis.Molecular docking of dihydroartemisinin with the core targets were performed by AutoDock software.CAL-27 cells were treated with different concentrations of dihydroartemisinin,and cell viability was detected by CCK-8.RT-qPCR was used to detect the expression level of core target mRNAs.Results 148 drug treatment targets were obtained,including 7 core targets.GO analysis showed that there were a total of 601 entries involved in the intersection targets,including protein kinase activity,protein tyrosine kinase activity,etc.Molecular doc-king suggests that KEGG enrichment analysis showed that the intersection targets involved 167 signaling pathways,inclu-ding Pathways in cancer,PI3K-Akt signaling pathway,etc.Molecular docking suggests that dihydroartemisinin could bind well to the core targets.CCK-8 results showed that dihydroartemisinin could inhibit the activity of CAL-27 cells significant-ly in a dose-dependent manner.RT-qPCR results showed that under the action of a certain concentration of dihydroartemis-inin,the mRNA expression of SRC,PIK3R1,PIK3CA and PTPN11 in cells decreased.Conclusion Dihydroartemisinin may play an anticancer role in oral squamous cell carcinoma by acting on multiple targets such as SRC and PIK3R1.
Objective Network pharmacology and molecular docking were used to study the possible mechanism of dihydro-artemisinin in the treatment of oral squamous cell carcinoma,and the core targets were experimentally verified.Methods The targets of dihydroartemisinin were obtained through PharmMapper and other databases,and GeneCards and other data-bases were used to obtain the disease targets of oral squamous cell carcinoma.The intersection targets were the potential tar-gets of dihydroartemisinin treating oral squamous cell carcinoma.The potential target protein-protein interaction network was established through the STRING database,and the data processed by CytoScape software and screened for core targets.Metascape was used for GO and KEGG enrichment analysis.Molecular docking of dihydroartemisinin with the core targets were performed by AutoDock software.CAL-27 cells were treated with different concentrations of dihydroartemisinin,and cell viability was detected by CCK-8.RT-qPCR was used to detect the expression level of core target mRNAs.Results 148 drug treatment targets were obtained,including 7 core targets.GO analysis showed that there were a total of 601 entries involved in the intersection targets,including protein kinase activity,protein tyrosine kinase activity,etc.Molecular doc-king suggests that KEGG enrichment analysis showed that the intersection targets involved 167 signaling pathways,inclu-ding Pathways in cancer,PI3K-Akt signaling pathway,etc.Molecular docking suggests that dihydroartemisinin could bind well to the core targets.CCK-8 results showed that dihydroartemisinin could inhibit the activity of CAL-27 cells significant-ly in a dose-dependent manner.RT-qPCR results showed that under the action of a certain concentration of dihydroartemis-inin,the mRNA expression of SRC,PIK3R1,PIK3CA and PTPN11 in cells decreased.Conclusion Dihydroartemisinin may play an anticancer role in oral squamous cell carcinoma by acting on multiple targets such as SRC and PIK3R1.