[Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways].

Objective: To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang (SC) root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.

Methods: The targets of SC and pancreatic cancer were predicted using the network pharmacological database, the protein-protein interaction network was constructed, and pathways, functional enrichment and molecular docking analyses were performed. CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines, and its effects on invasion, migration, proliferation, and apoptosis of pancreatic cancer cells were evaluated. Western blotting was performed to verify the results of network pharmacology analysis.

Results: We identified a total of 18 active components in SC, which regulated 21 potential key targets in pancreatic cancer. GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation, signal transduction, and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways. Among the 8 cancer cell lines, The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells, and significantly inhibited the invasion, migration, and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells (P < 0.05). Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells (P < 0.001).

Conclusion: The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.