| Lung cancer is the most common cancer in the world.It is the first cause of cancer and cancer death in China.Advanced non-small cell lung cancer is most common,and 5-year survival rate is still low.In recent years,despite the continuous development of treatment methods,chemotherapy is still the main treatment of advanced NSCLC in China.The most commonly used is paclitaxel combined with platinum chemotherapy.However,the "treatment bottleneck" caused by drug resistance has not been overcome,limiting its clinical benefits.The intervention of Chinese traditional Chinese medicine on chemotherapy resistance of tumor has been paid more and more attention by researchers.It is still of practical significance and practical value to systematically screen the active ingredients of traditional Chinese medicine by using large data analysis method and to verify its possible reversal of chemotherapeutic drug resistance through more scientific experimental methods,so as to increase the effect of chemotherapeutic drugs.In order to understand the current situation and development trend of drug resistance research in chemotherapy and targeted therapy of lung cancer at home and abroad,used the visual analysis method of evidence-based medicine(EBM)to analyze the Chinese and English literatures related to this research field in an all-round way.The Chinese literatures of Chinese biomedical database,Chinese knowledge website,Wanfang database and English literatures of Pub Med,EMbase,The Cochrane Library database related to the feild of study were searched by computer.According to the criteria of inclusion and exclusion,documents were selected and extracted and sorted out by BICOMS-2 analysis software,and theco-occurrence matrix and word matrix were generated.The network map and cluster analysis were drawn by Net Draw 2.089 and g CLUTO 1.0.A total of 1250 articles were screened and included in the study of chemotherapy resistance of lung cancer in China.Publications began in 1996,and then increased year by year.At present,there were four main research hotspots.A total of 2893 English documents were included;the publications began in 1995 and peaked in 2015.There were 1398 major topics included in the articles.Among them,Lung Neoplasms,Drug Resistance,Neoplasm,Antineoplastic Agents,Non-Small-Cell Lung Carcinoma,Epidermal Growth Factor Receptor were in the core position.The research topics included four aspects such as paclitaxel and other plant-derived anti-tumor agents in the treatment of lung cancer multi-drug resistance mechanism and so on.Studies on drug resistance in molecular targeting therapy for lung cancer have been carried out for more than 20 years in Chinese and English literature.The research focus focusesed on the mechanism of molecular targeting drug resistance.The results showed that the drug resistance of lung cancer had been paid more and more attention in recent ten years,especially in the last five years.The main research focus focusesed on the possible molecular mechanisms of NSCLC resistance and paclitaxel resistance.On the basis of this study,we studied the reversal of NSCLC paclitaxel resistance by traditional Chinese medicine.In order to understand the current research status of Chinese traditional medicine in reversing chemotherapy resistance and the characteristics of traditional Chinese medicine selection,BICOMS analysis software and Ucinet 6.0 software were used to analyze systematically and visually the literature on reversing chemotherapy resistance of traditional Chinese medicine.A total of 977 literatures conforming to the inclusion exclusion criteria were screened out.Through information extraction,a total of 19 categories and 261 herbs Chinese medicines were screened out.The results of the analysis of the whole traditional Chinese medicine were as follows: in all the traditional Chinese medicine,the drugs such as tetrandrine,flavescent sophora root,flavescent sophora root,ginseng,kawagana and codonopsis pilosula had more application in the study of the reverse chemotherapy resistance,among which Fangji was the most potential Chinese medicine in this field.Therefore,Fangj was selected as a potential drug to reverse NSCLC paclitaxel resistance in this study.In order to screen the active components and corresponding targets of Fangji,a traditional Chinese medicine,network pharmacology and TCMSP database were usedto search the chemical constituents of Fangji.The drug-like(DL)? 0.18 was set to screen out the active components of Fangji,and the corresponding targets were searched and sorted out by Swisstarget database.Construction of the active component-Target Network of Fangji,target protein interaction network(PPI).Target GO(gene ontology)function enrichment and KEGG signaling pathway enrichment were carried out on DAVID website.15 main active components of Fangji were collected,105 corresponding targets and 67 biological processes in vivo.Among them,there are 8 medicinal components related to NSCLC and 3 corresponding targets.In order to explore the medicinal components that may reverse the drug resistance of NSCLC paclitaxel in Fangji and its possible mechanism,RTCA technique was used to verify respectively the inhibitory effect of 8 medicinal components of Fangji on the proliferation of A549/PTX.It was found that ?-sitosterol,Dichotomitin,menispermine and other components had inhibitory effect on the proliferation of A549/PTX.Therefore,?-sitosterol was used to interfere with A549/PTX,and the gene expression was screened by high-throughput sequencing of expression profile.Combined with the results of network pharmacology,Q-PCR,Western BLOT,flow cytometry and laser confocal technique were used.Some related genes were verified.The results showed that ?-sitosterol could down-regulate the HSP90,KLK3 gene in AR/HSP90 signaling pathway of A549/PTX cells and up-regulate the CASP9 ? CASP3 ? BCL2 ? BAX gene in mitochondrial / CASP9 apoptosis signaling pathway.It can be seen that ?-sitosterol in Fangji can reverse the drug resistance of paclitaxel in NSCLC to a certain extent. |
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