Exploration of the therapeutic mechanism of Yiqi Jiedu recipe for treatment of primary liver cancer based on network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To explore the effective components of Yiqi Jiedu recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of primary liver cancer through network pharmacology and molecular docking approaches.@*METHODS@#TCMSP, Uniport, Genecards and String databases were searched to obtain the target genes of drugs and disease using Cytoscape 3.8.2 software. GO and KEGG enrichment analyses were performed to identify the common genes in the target genes of the drugs and disease. Using Pubcham, RCSB and Autoduck, the effective components of the drugs were connected with the final core genes. The effects of different concentrations of Yiqi Jiedu recipe on the expressions of the core genes DHX9, HNRNPK, NCL and PABPC1 in HepG2 cells were analyzed with Western blotting and real- time fluorescence quantitative PCR.@*RESULTS@#We finally identified 8 core genes from the drug and disease targets, including DDX5, HNRNPK, PABPC1, DHX9, RPS3A, RPS3, RPL13, and NCL. GO analysis showed that these core genes were involved mainly in the biological processes of adrenaline receptor signal communication, movement of cellular or subcellular components, blood particles, adhesion class and iron ion binding. KEGG analysis showed that the Ras signaling pathway had the greatest gene enrichment. The results of molecular docking suggested that the effective components of the recipe were capable of docking with the core genes under natural conditions, and PABPC1 and stigmasterol had the highest binding energy. In HepG2 cells, treatment with 10% medicated serum for 48 h had the strongest effect on the expression of DHX9, HNRNPK, NCL and PABPC1 (P < 0.05).@*CONCLUSION@#Yiqi Jiedu recipe is capable of regulating viral expression of primary liver cancer multiple effective components that bind to DHX9, HNRNPK, NCL and PABPC1.

Anti-tumor Effects of Yiqi Jiedu Recipe and Analysis of Its Bioinformatics / 广州中医药大学学报

Objective To observe the inhibitory effects of Yiqi Jiedu Recipe(YJR)on transplanted Lewis lung cancer in mice and to explore its relative mechanism. Methods In-vivo mouse model of transplanted Lewis lung cancer was established. Twenty modeled mice were divided into model group,low- and high-dose YJR groups, and cisplatin group, 5 mice in each group. After treatment, the mouse general situations, body mass, body mass excluding tumor mass,tumor mass,tumor index,tumor volume,and tumor-inhibition rate were detected. In the in-vitro experiments, the inhibitory effect of YJR on the proliferation of A549 and H1299 cells was evaluated by CCK8 assays, and the effect of YJR on the apoptosis of A549 and H1299 cells was evaluated by flow cytometry assay. Bioinformatics analysis was carried out to identify the critical function,pathways and genes with bioinformatics mining method. Results Compared with the model group, high-dose YJR group and cisplatin group significantly inhibited the tumor growth of the transplanted Lewis lung cancer in mice(P<0.05 or P < 0.001). The experimental results in vitro showed that YJR significantly inhibited lung cell growth, and induced lung cell apoptosis. Bioinformatics analysis results showed that the inhibitory effects of YJR was probably related to multiple paths including apoptosis,cell cycle,autophagy,etc.,and promoting apoptosis may be the important way. YJR played a role in promoting apoptosis via AKT, HSP90, BCL2, CASP9 and activation of PI3K-AKT pathway. Conclusion YJR exhibits anti-tumor actions through regulating the targets AKT,HSP90, BCL2, CASP9 and affecting PI3K-AKT pathway to promote apoptosis and inhibit cell proliferation, thus to suppress the growth of transplanted tumor.