Study on the Potential Molecular Mechanism of Xihuang Pill in the Treatment of Pancreatic Cancer Based on Network Pharmacology and Bioinformatics.

OBJECTIVE

We aimed to analyze the possible molecular mechanism of Xihuang pill (XHP) in the treatment of pancreatic cancer based on methods of network pharmacology, molecular docking, and bioinformatics.

METHODS

The main active components and targets were obtained through the TCMSP database, the BATMAN-TCM database, and the Chemistry database. The active ingredients were screened according to the "Absorption, Distribution, Metabolism, Excretion" (ADME) principle and supplemented with literature. We searched GeneCards, OMIM, TTD, and DrugBank databases for pancreatic cancer targets. The targets of disease and ingredients were intersected to obtain candidate key targets. Then, we constructed a protein-protein interaction (PPI) network for protein interaction analysis and a composition-key target map to obtain essential effective ingredients. Metascape was used to perform functional enrichment analysis to screen critical targets and pathways. The expression and prognosis of key targets were examined and analyzed, and molecular docking was carried out.

RESULTS

A total of 52 active ingredients of XHP, 121 candidate targets, and 52 intersecting targets were obtained. The core active ingredients of XHP for the treatment of pancreatic cancer were quercetin, 17--estradiol, ursolic acid, and daidzein. The core targets were EGFR, ESR1, MAPK1, MAPK8, MAPK14, TP53, and JUN, which were highly expressed genes of pancreatic cancer. Among them, EGFR and MAPK1 were significantly correlated with the survival of pancreatic cancer patients. The key pathway was the EGFR/MAPK pathway. The molecular docking results indicated that four active compositions had good binding ability to key targets.

CONCLUSION

The molecular mechanism of XHP for the treatment of pancreatic cancer involved multiple components, multiple targets, and multiple pathways. This research theoretically elucidated the ameliorative effect of XHP against pancreatic cancer and might provide new ideas for further research on the treatment of pancreatic cancer.