| Objective: To retrospective analyze and summarize the core drug combination for treating breast cancer bone metastasis with the help of TCMISS,and apply network pharmacology to predict the mechanism of action of core drug combination for treating breast cancer bone metastasis.To evaluate the clinical effect of Professor Song Aili’s core drug combination(Bushen Huoxue Zhuanggu Prescription)in treating breast cancer bone metastasis through clinical research.So as to provide a foundation for the inheritance and further research of famous TCM doctor Song Aili’s academic thoughts.Methods: In the data mining research,through the Hospital’s clinical scientific research big data search platform,TCM prescriptions of breast cancer bone metastasis patients treated by Professor Song Aili in Affiliated Hospital of Shandong University of TCM from June 2019 to June 2022 were collected.TCMISS was used to analyze its drug frequency,four characteristics,five favors,channel tropism and the core drug combination.In the network pharmacology research,the active ingredients and corresponding targets of the core drug combination are queried through the TCMSP database,and the related targets of breast cancer bone metastasis were searched in the Gene Cards and OMIM databases.The STRING database was used for PPI analysis,and the Metascape database was used for GO and KEGG enrichment analysis.In the clinical research,According to inclusion and exclusion criteria,breast cancer bone metastasis patients treated by Professor Song Aili at Affiliated Hospital of Shandong University of TCM were randomly divided into control and treatment group.The control group was given zoledronic acid,the treatment group was given Bushen Huoxue Zhuanggu Prescription and zoledronic acid.The changes and differences of pain score,Karnofsky score,TCM syndrome quantitative score,blood calcium and ALP,and tumor markers CEA,CA153,CA125 levels were compared between the two groups before and after treatment.Results: In the data mining research,A total of 145 TCM prescriptions were screened,The top six drugs used frequency were Fructus Psoraleae,Radix Notoginseng,Fructus Lycii,Radix Astragali,Codonopsis Pilosula and Rhizoma Curcumae.The most frequently used drugs were tonifying kidney and promoting blood circulation drugs.The drug properties were mainly warm and flat,the drug tastes were sweet and bitter,and the channel tropisms were liver,spleen,kidney.Ten drugs which were Fructus Psoraleae,Fructus Lycii,Radix Notoginseng,Hedyotis diffusa,Rhizoma Curcumae,Radix Astragali,Codonopsis Pilosula,Radix Glycyrrhizae,Poria,Radix Angelicae Sinensis founded by association rules network were the core drug combination for the treatment.In the network pharmacology research,157 components and 262 targets of the core drug combination were obtained,including quercetin,Stigmasterol,beta-sitosterol,kaempferol,7-Methoxy-2-methyl isoflavone.There were 4708 related breast cancer bone metastasis targets.215 targets were obtained by mapping the drug and the disease targets,involved AKT1,MAPK3,TP53,MAPK1,STAT3 etc.Go analysis showed that biological processes were concentrated in the progress of cellular response to organic cyclic compound,response to hormone,cellular response to lipid,response to xenobiotic stimulus,response to inorganic substance etc.Cell components were mainly involved in membrane raft,transcription regulator complex,vesicle lumen,receptor complex,endoplasmic reticulum lumen etc.Molecular functions were involved in nuclear receptor activity,protein domain specific binding,kinase binding,protein homodimerization activity,oxidoreductase activity etc.KEGG analysis showed that the pathway related to breast cancer bone metastasis mainly involved in PI3K-Akt signaling pathway,Fox O signaling pathway,NF-kappa B signaling pathway,JAK-STAT signaling pathway and Calcium signaling pathway etc.In the clinical research,50 breast cancer bone metastasis patients were included.During the course of treatment,2 patients in control group and 1 patient in treatment group dropped out due to unscheduled treatment.There was no statistically difference between the two groups’ patients in baseline analysis(P>0.05).The curative effect of the treatment group was better than the control group in reducing the pain score,increasing the Karnofsky score,and reducing TCM syndrome quantitative score have statistically difference(P < 0.05).In regulating blood calcium,ALP,CEA,CA153,CA15 before and after treatment,there was no statistical significance in comparison between groups or within groups(P>0.05).Conclusion: Professor Song Aili’s TCM prescription in treating breast cancer bone metastasis taking “tonifying kidney and promoting blood circulation” as core treatment method.Fructus Psoraleae,Fructus Lycii,Radix Notoginseng,Hedyotis diffusa,Rhizoma Curcumae,Radix Astragali,Codonopsis Pilosula,Radix Glycyrrhizae,Poria,Radix Angelicae Sinensis are the core drug combination.The core drug combination for the treatment of breast cancer bone metastasis involves multi-component,multi-target and multi-pathway.Bushen Huoxue Zhuanggu Prescription combined with zoledronic acid in the treatment of breast cancer bone metastasis can effectively relieve bone pain,improve the TCM symptoms and the quality of patient’s life. |