Study On The Mechanism Of Hedyotis Diffusa Willd In The Treatment Of Non-small Cell Lung Cancer Based On Systems Pharmacology

Objective:Cancer is a major disease that seriously affects people's health,and non-small cell lung cancer(NSCLC)is one of the malignant tumors with the highest mortality,and there is a lack of effective treatment and drugs.In this study,a systems pharmacology research method was used to analyze the active components and mechanism of traditional Chinese medicine,which has a wide range of anticancer effects,such as Hedyotis diffusa Willd(HDW).It provides a new idea for the treatment of non-small cell lung cancer with traditional Chinese medicine.Methods:(1)Lewis lung cancer model was used,and Hedyotis diffusa Willd was administered with different concentrations(10mg/kg,20mg/kg,and 40mg/kg).The tumor size,weight and survival time of mice were observed,and the levels of TNF-?and IL-1?in serum were measured by Enzyme-Linked ImmunoSorbent Assay(ELISA).The expression of CD8~+T cells,Treg cells and natural killer cells(NK)cells in tumor tissues were analyzed by flow cytometry.(2)According to the pharmacokinetic characteristics of absorption,distribution,metabolism and excretion(ADME)of in vivo,the potential active components of Hedyotis diffusa were screened,and the candidate targets of active compounds were obtained by TCMSP target prediction method.The biological process of the active compound was constructed by gene enrichment analysis,the active compound-target network was constructed by combining the information of the active compound and the potential target,and the potential targets obtained from Hedyotis diffusa were mapped to the DAVID database.The results of enrichment analysis of access pathway,combined with the enrichment analysis of target and corresponding pathway,constructed the target-pathway network;at the pathway level,in order to study the mechanism of action of Hedyotis diffusa,an integrated non-small cell lung cancer pathway was constructed.(3)The expression of target protein induced by kaempferol at different concentrations(10?mol/L,20?mol/L,30?mol/L,40?mol/L)of lung cancer cell line H1975 was detected by Western Blot.Results:(1)Hedyotis diffusa Willd could inhibit the tumor growth and prolong the survival time of tumor-bearing mice,ELISA results showed that Hedyotis diffusa could reduce the expression of TNF-?and IL-1?in serum,flow cytometry analysis showed that Hedyotis diffusa could inhibit the tumor growth and prolong the survival time of tumor-bearing mice.Hedyotis diffusa can increase the expression of CD8~+T cells and NK cells and decrease the expression of Treg cells in tumor cells,which shows that Hedyotis diffusa can improve the anti-tumor effect.(2)Through the ADME evaluation of drugs,26 potentially bioactive components were screened out,and 151 potential targets were obtained by target prediction method.According to the correlation analysis of the gene ontology biological process involved by the target of Hedyotis diffusa,many targets are involved in the positive regulation of cell proliferation,the positive regulation of MAPK kinase activity,nitric oxide biosynthesis and inflammatory response.The results showed that the screened bioactive components regulated multiple targets,and through the topological analysis of target-pathway network,it was found that the corresponding targets of the compounds could be connected to many different pathways.Including cancer signal pathway,PI3K-Akt signal pathway,MAPK signal pathway,VEGF signal pathway,reflecting the characteristics of multi-channel regulation;by modularizing the network diagram,we mainly get three treatment modules,all of which are closely related to non-small cell lung cancer.(3)Western Blot assay confirmed that the potential bioactive components had killing effect on tumor cells,down-regulated the expression of integrated pathway proliferation,migration and inflammation module target protein,thus inhibiting the occurrence,development and migration of tumor cells.Conclusion:To sum up,based on the systems pharmacology research methods,this paper discusses the effects of Hedyotis diffusa Willd Chinese herbal medicine on anti-inflammation,anti-proliferation and anti-migration by regulating immunity in a variety of ways,so as to achieve the purpose of treating non-small cell lung cancer.