Mechanism Exploration And Clinical Evaluation Of Didangtang In Treatment Of Bladder Cancer Based On Network Pharmacology

Objective:To explore the target and possible mechanism of the treatment of Bladder Cancer by Didangtang,and to provide clinical application basis for treatment of bladder cancer with Didangtang decoction.Methods:(1)The study collected a total of 44 patients with bladder cancer in urology clinics and inpatients of Jiangsu Provincial Hospital of Traditional Chinese Medicine.They were randomly divided into a treatment group and a control group,with 22 patients in each group.In the control group,bladder gemcitabine was infused chemotherapy once a week.In the treatment group,infusion chemotherapy was given.In addition,the treatment group was given Didangtang orally,1 dose daily,and served warm after breakfast and dinner.The two groups were treated for 3 months.Recurrence rate,clinical symptoms,quality of life and safety would be compared.(2)Based on multiple databases of traditional Chinese medicine and diseases,use network pharmacology to screen potential targets,analyze the biological functions of potential targets,and build a "Chinese medicine-target-pathway-disease" relationship network.The bioinformatics method was used in the population and gene database to explore the differential expression of core targets in tissues,the distribution in the population,and the correlation with prognosis.(3)In vitro experiments were used to verify the function of Didangtang decoction,and the mechanism of Didangtang decoction on candidate targets was tested.Results:(1)A total of 44 patients were included in the study.They were randomly divided into the Didangtang group and the control group.All patients completed the treatment cycle and follow-up questionnaire according to the treatment plan.There was no significant difference in the distribution of population characteristics between the two groups of patients.In the first scale score,the two groups were significantly better than the reference values in physical function,role function,and emotional function.The scores for weakening these aspects were significantly lower than the reference values and were higher than the reference values in terms of constipation and economic difficulties,and there was no significant difference between the two groups.Comparing the scores of the patients before and after treatment,it was found that the Didangtang group had significant improvements in the five functional areas of physical function,role function,emotional function,social function,and overall health.The four symptom areas of financial hardship are also alleviating.In addition,compared with the control group,the scores in the three symptom areas of nausea,vomiting,decreased appetite,and constipation was also significantly reduced in the patients of the Didangtang group.Comparison of the scores after treatment between the two groups shows that,compared with the control group,the patients have significantly improved physical function and constipation symptoms after the continuous taking of Didangtang.In addition,in the score for the specific scale for non-muscle invasive bladder cancer,there was no significant statistical difference between the two groups of patients at the first inquiry.After treatment,the two groups of patients had significant improvements in urinary tract symptoms,treatment problems,future concerns,and bowel problems.At the same time,after the treatment,the scores of the two groups patients were further analyzed.We found that the urinary tract symptoms,treatment problems,and intestinal problems of the patients in the Didangtang group had more significant improvement than the control ones;(2)A total of 21 core target genes(MTOR,AR,MMP9,CSF2,ALB,FN1,FASLG,JUN,CREB1,CXCL8,ERBB2,CDH1,EGFR,TP53,CDKN2A,PTGS2,MMP2,FLT1,VEGFA,MMP3,PLAU)and 16 high enriched pathways were screened out.Among them,4 molecular functional plates(enzyme binding,specific protein binding,contact reactivity,protein binding),4 cells constitute a plate(cytoplasmic vesicles,extracellular space,extracellular region,vesicle cavity),and 4 biological process plates(Cell response to chemical stimulus,chemical reaction,drug response,oxygenate response)and 16 pathways(bladder cancer pathway,cancer pathway,cancer microRNA,endocrine resistance,proteoglycan in cancer,Kaposi’s sarcoma-associated herpes Viral infection,rheumatoid arthritis,transcriptional disorders in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,relaxin signaling pathway,MAPK signaling pathway,HIF-1 signaling pathway,fluid shear stress.And atherosclerosis,platinum resistance).A functional network of Didangtang was constructed systematically.At the same time,six targets,cadherin 1(CDH1),CAMP responsive element binding protein 1(CREB1),colony stimulating factor 2(CSF2),AP-1 transcription factor(JUN),matrix metalloproteinase 2(MMP2),and prostaglandin-endoperoxide synthase(PTGS2),were differentially expressing in bladder cancer tissues(P<0.05).Furthermore,JUN and MMP2 were also differentially distributed in the population(P<0.05).(3)At the same time,the expression level of JUN was associated with the prognosis of patients with bladder cancer(P=0.017).The in vitro experiment revealed that the Didangtang inhibited the proliferation of bladder cancer cells and decreased the expression of candidate target JUN(P<0.01).Research conclusion:Clinical observation confirmed that Didangtang can improve the quality of life of patients with non-muscle invasive bladder cancer.The treatment of bladder cancer has the characteristics of multiple targets and multiple pathways.Among them,we have initially confirmed that the Didangtang can repress the expression of the target JUN and inhibit the proliferation of bladder cancer cells.Our study lied with a good foundation for further mechanism research.