基于网络药理学探讨九痛丸治疗肺癌胸痛可行性验证分析  

Effect of Jiutong Pills on the treatment of chest pain in patients with lung cancer based on network pharmacology:a feasibility study

作　　者：张亚萌 宋鲁成 ZHANG Ya-meng;SONG Lu-cheng(The Fivst Affiliatad Hospital of Shandong Fivst Medical Chiversity,Jinan Shandong 250000)

机构地区：[1]山东第一医科大学第一附属医院

出　　处：《世界中西医结合杂志》2020年第2期203-208,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：山东省中医药管理局项目(2013-197)

摘　　要：现代医家临床应用九痛丸多依据《金匮要略》中“治九种心痛”的注解用以治疗心系疾病所致的心胸疼痛,但由于其用药峻猛,理论上与心系疾病常见的气虚血瘀、痰湿毒邪内阻的发病机理并不完全符合,因此临床研究较少。宋鲁成教授在临床诊疗中发现,九痛丸可能是张仲景治疗癌性胸痛的处方,效用极佳,但是近现代文献中尚未有人对九痛丸与治疗肺癌进行系统的研究。因此文中基于网络药理学和生物信息学等方法,研究应用九痛丸治疗肺癌胸痛的具体作用通路与可能机制,并通过实验验证九痛丸治疗肺癌胸痛的理论以及可行性。文章主要通过药理学数据库检索,得到九痛丸药物组成中的活性成分及对应靶点,然后再挖掘肺癌已知发病相关基因靶点,将药物与疾病靶点做成靶点网络后取交集进行分析,筛选九痛丸与肺癌相关性最强的特异性靶点并进行信号通路富集分析,显示九痛丸作用于肺癌的关键节点涉及的信号通路主要被富集在细胞周期调控、细胞增殖、凋亡、肿瘤转录调控失调、病毒致癌及其他肿瘤通路等100余条信号通路。筛选其中肿瘤细胞周期调控这一关键作用机制,选择人肺癌细胞(SPC-A1)进行实验验证,结果发现流式细胞分析显示九痛丸可明显抑制SPC-A1的增殖,明显促进其凋亡。提示九痛丸能通过抑制肿瘤细胞增殖来治疗肺癌。Jiutong Pills is considered as“treating nine kinds of heart pain”according to the Essentials from the Golden Cabinet(Jin Gui Yao Lue)by many modern physicians and thus it is often used to treat chest pain caused by heart diseases.However,this formula contains medicinals strong in property,and it is not consistent with the pathogenesis of qi deficiency,blood stasis,internal obstruction of phlegm dampness and toxin,which is commonly seen in the heart diseases.Professor Song Lucheng put forward that Jiutong Pills may be a prescription of Zhang Zhongjing for treating chest pain caused by lung cancer with a good clinical effect.However,there was no systematic research on Jiutong Pills and lung cancer in modern literature.Based on the methods of network pharmacology and bioinformatics,this paper investigated the action pathways and possible mechanism of Jiutong Pills in treating lung cancer chest pain and verified the hypothesis and feasibility through experiments.The active components and corresponding targets of Jiutong Pills were obtained by searching pharmacology databases,and the known target genes of lung cancer were found.Then the drugs and disease targets were made into a network of targets,and the intersections of drugs and disease targets were analyzed.The specific targets with strongest correlation between Jiutong Pills and lung cancer were screened and signal pathway enrichment analysis showed that the key nodes of Jiutong Pills acting on lung cancer were mainly concentrated in more than 100 signal pathways such as cell cycle regulation,cell proliferation and apoptosis,tumor transcriptional regulation disorder,viral carcinogenesis,other tumor pathways.The key mechanism of tumor cell cycle regulation was screened,and human lung cancer cells(SPC-A1)were selected for experimental verification.Flow cytometry showed that Jiutong Pills could significantly inhibit the proliferation of SPC-A1 and promote its apoptosis.In conclusion,Jiutong Pills can be used to treat lung cancer by inhibiting tumor cell prolifer

关 键 词：九痛丸 肺癌 网络药理学 肿瘤细胞周期 

分 类 号：R256.22[医药卫生—中医内科学]