Abstract:
Objective: To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma (HCC) based on network pharmacology and transplanted liver cancer rat model. Methods: TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets, and databases including Gene Cards, OMIN, Drugbank and TTD were further used to collect HCC‑related drug targets. The intersecting targets were obtained by mapping the drug and disease targets. The component‑targets network was constructed and visualized by Cytoscape 3.8.2 software. Protein‑protein interaction (PPI) network was built by STRING online platform, and the topological relationship and core targets were analyzed and screened by using CytoNCA software. In addition, Metascape database was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. At last, A transplanted liver cancer rat model was established by using Walker‑256 cell line and treated by AiTongXiao granule for 15 days. Western blot was used to further compare the expression levels of AKT, pAKT, p53, p‑p53, ERK1/2 and ERK1/2 in the tumor between the treatment group and the control group.Results:A total of 257 active components were obtained from AiTongXiao granule, corresponding to 294 drug targets. Meanwhile, 231 of the 7 993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets. Eleven core targets including AKT1, IL6, TP53, MAPK3, TNF, JUN , CASP3,MAPK1,MYC,PTGS2 and MMP9 were further obtained by median screening. GO and KEGG analysis results showed that these core targets enriched to HBV, TNF and cancer related pathways. The rat transplanted liver cancer model results indicated significant downregulation for AKT, p‑AKT, pERK1/2, and significant upregulation of p‑p53 after AiTongXiao granule treatment (P<0.05).Conclusion: AiTongXiao granule could act to multiple cancer related pathways, and AKT, p53 and ERK1/2 were validated to be regulated by ATXF in rat model. The mechanism may be through the regulation of the above signaling pathways to exert anti‑liver cancer effect.