基于网络药理学探讨硒参芝方治疗食管癌的药效作用机制及关键调控通路的验证  

Exploring mechanism of action and validation of key regulatory pathways of selenshenzhi prescription in treatment of esophageal cancer based on network pharmacology

作　　者：纪柯伊 吴宿慧[1,2] 远佳瑶 李寒冰 王顺才[3] 王龙杰 王琳琳 高启龙 JI Ke-yi;WU Su-hui;YUAN Jia-yao;LI Han-bing;WANG Shun-cai;WANG Long-jie;WANG Lin-lin;GAO Qi-long(Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;Engineering Research Center of Healthy Aging Industry of Henan Province,Zhengzhou 450046,China;Henan Puhui Tiancheng Biotechnology Co.,LTD,Zhengzhou 450046,China;Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南省健康衰老产业工程研究中心,河南郑州450046 [3]河南普惠天成生物科技有限公司,河南郑州450046 [4]郑州大学附属肿瘤医院,河南郑州450046

出　　处：《中国药理学通报》2024年第11期2174-2184,共11页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No U1904152);河南省科技攻关计划(No 232102311191)。

摘　　要：目的利用网络药理学和体内外实验,研究硒参芝方抗食管癌的主要活性成分和潜在作用机制。方法利用TCMSP、OMIM和GeneCards数据库提取共同靶位,再利用STRING数据库进行PPI网络构建。使用DAVID数据库进行GO和KEGG富集分析,基于STRING和DAVID数据库构建网络,进行体内外实验验证。结果预测结果共获得硒参芝方活性成分100个、相关靶点749个,硒参芝方与食管癌的共同靶点168个,参与PI3K-AKT信号通路、癌症中的蛋白聚糖等信号通路发挥作用;体外实验将硒参芝方对人食管癌EC9706进行相关靶点的初步验证,结果表明硒参芝方可明显抑制食管癌细胞增殖并通过Bax、Bcl-2、Caspase-3等凋亡关键蛋白的表达来诱导EC9706凋亡。最后体内动物实验将硒参芝方对食管癌裸鼠进行核心靶点和通路的初步验证,结果表明硒参芝方可明显抑制肿瘤的增殖,促进肿瘤细胞凋亡,并通过调控PI3K/AKT信号通路上的关键蛋白的表达来诱导肿瘤凋亡。结论硒参芝方通过多成分、多靶点、多通路协同作用控制食管癌的发生发展,为今后临床进一步探讨硒参芝方治疗食管癌的机制提供理论依据。Aim To study the main active components and potential mechanism of selenshenzhi prescription against esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The common target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was constructed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verification.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were obtained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenzhi prescription was used to conduct preliminary verification of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic proteins.Lastly,the core target and pathway of selenshenzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esophageal cancer.The results showed that selenshenzhi prescription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apoptosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selenshenzhi prescription can control the occurrence and development of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

关 键 词：硒参芝方 食管癌肿瘤 网络药理学 分子机制 PI3K-AKT信号通路 作用机制 

分 类 号：R285[医药卫生—中药学]