Professor Hu Kaiwen's Medication Rule And Related Mechanism Prediction Research In The Treatment Of Non-small Cell Lung Cancer

OBJECTIVE:To explore Professor Hu Kaiwen’s experience in the treatment of NSCLC and analyze the mechanism of the core drug group in the treatment of NSCLC.METHODS:1.Data mining part.Collecting and collating of Professor Hu Kaiwen’s prescriptions for the treatment of NSCLC in the outpatient clinic of Oriental Hospital of Beijing University of traditional Chinese Medicine from September 2019 to September 2020,using Excel 2016,SPSS Modeler 18,0 and SPSS Statistics 24.0 software,we carried on the data mining by frequency statistics,association rules and cluster analysis of the outpatient prescription in accordance with the standard,in order to summarize the medication characteristics of Professor Hu Kaiwen in the treatment of NSCLC and obtain the core drug group.2.Analysis of network pharmacology.The active components and potential targets of the core drug group were obtained through the traditional Chinese medicine database and literature supplement,and the disease targets related to NSCLC were obtained by searching the disease database.Protein-protein interaction analysis and functional enrichment analysis were performed on disease-drug intersection targets to predict the molecular mechanisms of core drugs acting on NSCLC,such as targets,biological processes and signal pathways.The target map of protein-protein interaction,core module diagram and "drug-disease-target-pathway" network diagram were visually drawn by Cytoscape 3.6.0 software,and the network data were analyzed.RESULTS:(1)A total of 166 prescriptions and 117 kinds of traditional Chinese medicine were included in Hu Kaiwen’s outpatient clinic for the treatment of non-small cell lung cancer.(2)The first ten high frequency drugs are Prepared rehmannia glutinosa,Angelica sinensis,Glycyrrhiza uralensis,Radix Astragali,Poria,Ginger,Bamboo shavings,Centipede,Beehive and Ophiopogon.The most common siqi of prescreption is warm;the number of sweet drugs is the most,followed by pungent drugs;the meridians of drugs are mainly into the lung,spleen and liver;the most deficiency-tonifying drugs are used.(3)The drug pairs obtained by association rules are "Prepared rehmannia glutinosa-Angelica-Radix Astragali","Prepared rehmannia glutinosa-Cinnamon-Poria cocos","Clove-Scorpion" and"Beehive-Centipede".(4)Four new drug groups were obtained by cluster analysis.They are "Centipede-Beehive","Ophiopogon-Paeonia lactiflora","Poria cocos-Fructus Aurantii-Bamboo shavings-Ginger-Trichosanthes-licorice","Angelica-Radix Astragali-Prepared rehmannia glutinosa-Cinnamon".(5)The drug group of "Angelica-Radix Astragali-Prepared rehmannia glutinosa-Cinnamon" was selected for further network pharmacological analysis.(6)A total of 42 active components and 297 potential targets are in the drug group.1584 disease targets are selected.The disease-drug intersection targets in non-small cell lung cancer included 143 targets.(7)The potential active components of the drug group:quercetin,kaempferol,D-alanine,7-O-methylisomucronulatol,eugenol,formononetin.(8)Core targets:MAPK1,AKT1,TP53,JUN and TNF.(9)Subnet:the core targets of Subnet 1 are E2F1,CDK1,CDK2,CDKN1A,PCNA and CCNA2.The core targets of Subnet 2 are AKT1,MAPK1,SRC,HSP90AA1,ESR1,MAPK8,RELA and EGFR.The core targets of Subnet 3 are IL-6,TNF,IL1B,IL4,CCL2 and CXCL8.(10)Enrichment results:the main KEGG signal pathways are cancer pathway,IL-17 signal pathway,PI3K-AKT signal pathway,EGFR-TKI drug resistance and cell senescence.The main biological processes are:response to inorganic substance,response to wounding,apoptotic signaling pathway,response to lipopolysaccharide,cellular response to organic cyclic compound and so on.The main cellular components are:vesicle lumen,serine/threonine protein kinase complex,membrane raft,transcription factor complex,extracellular matrix and so on.The main molecular functions are:protein kinase binding,transcription factor binding,protein kinase activity,ubiquitin-like protein ligase binding,protein homodimerization activity and so on.CONCLUSION:Professor Hu Kaiwen’s experience in treating NSCLC includes:(1)The onset of tumor is related to aging and metabolic disorder,and the treatment of NSCLC always revolves around the purpose of"promoting metabolism and anti-aging".(2)the physique of tumor patients is deficiency and cold syndrome of the whole body,positivism and heat syndrome of locality,disharmony between yin and yang,and mixed cold and heat.Local and systemic treatment is divided in the treatment of NSCLC,the whole body is treated with traditional Chinese medicine,focusing on warming and tonifying the five zang organs,the locality use of external treatment,direct removal of cancer;(3)The "guiyuan theory" of tumor treatment is put forward,and the syndrome type of upper heat and lower cold exists in the whole body of tumor patients,and fire does not return to yuan.The treatment should be based on tonifying yin and yang in the kidney and causing fire to return to yuan.(4)Tumor patients with disorder of qi,often appear the state of "clear and turbid coherence".The treatment should adjust the qi,raise clear and descend turbid,and take Tong as supplement;(5)The pathogenesis of tumor always belongs to the disorder of qi,and the fire not returning to yuan.The principle of treatment is to regulate the qi machine and arouse the fire to return to yuan.(6)Commonly used clinical prescriptions include:Yueju pill combined with Pinellia decoction,Wendan decoction,modified Yinhuo decoction,Chai Guijiang decoction,Shengmai Dihuang decoction,Huangqi Guizhi Wuwu decoction,Wumei Pill,Maimendong decoction and insect medicine.The drug group obtained by cluster analysis is "Angelica-Radix Astragali-Prepared rehmannia glutinosa-Cinnamon",which can exert its curative effect in non-small cell lung cancer with multi-component-multi-target-multi-pathway.This may be related to the inhibition of inflammatory reaction,inhibition of cell proliferation,regulation of immunity and reversal of multidrug resistance.