Abstract
OBJECTIVE: To explore the mechanism of PG against acute lymphoblastic leukaemia (ALL) by network pharmacology and experimental verification in vitro. METHODS: First, the biological activity of PG against B-ALL was determined by CCK-8 and flow cytometry. Then, the potential targets of PG were obtained from the PharmMapper database. ALL-related genes were collected from the GeneCards, OMIM and PharmGkb databases. The two datasets were intersected to obtain the target genes of PG in ALL. Then, protein interaction networks were constructed using the STRING database. The key targets were obtained by topological analysis of the network with Cytoscape 3.8.0 software. In addition, the mechanism of PG in ALL was confirmed by protein‒protein interaction, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Furthermore, molecular docking was carried out by AutoDock Vina. Finally, Western blotting was performed to confirm the effect of PG on NALM6 cells. RESULTS: PG inhibited the proliferation of NALM6 cells. A total of 174 antileukaemic targets of PG were obtained by network pharmacology. The key targets included AKT1, MAPK14, EGFR, ESR1, LCK, PTPN11, RHOA, IGF1, MDM2, HSP90AA1, HRAS, SRC and JAK2. Enrichment analysis found that PG had antileukaemic effects by regulating key targets such as MAPK signalling, and PG had good binding activity with MAPK14 protein (-8.9 kcal/mol). PG could upregulate the expression of the target protein p-P38, induce cell cycle arrest, and promote the apoptosis of leukaemia cells. CONCLUSION: MAPK14 was confirmed to be one of the key targets and pathways of PG by network pharmacology and molecular experiments.