Abstract
ABSTRACT
Pancreatic cancer has a dismal prognosis and limited therapeutic options, highlighting an urgent need for effective treatments. Sophoricoside (SOP), a natural isoflavone glycoside, has exhibited anticancer activities in multiple malignancies, including lung cancer, glioblastoma, and hepatocellular carcinoma. We combined cellular assays, network pharmacology, machine learning, and multi‐omics to investigate SOP's effects. SOP‐inhibited proliferation of MIA PaCa‐2, SW1990, and PANC‐1 cells dose‐dependently. Network pharmacology revealed 85 overlapping targets enriched in MAPK, apoptosis, and PD‐L1/PD‐1 pathways. Machine learning and differential expression identified PTPN1 as the core target.
PTPN1
was markedly upregulated in pancreatic adenocarcinoma, and its high expression correlated with poor survival and immune infiltration. Functional enrichment linked
PTPN1
to TGF‐β, VEGF, and metabolic reprogramming. Molecular docking suggested a possible binding mode between SOP and PTPN1, involving four predicted hydrogen bonds. SOP reduced
PTPN1
mRNA, and
PTPN1
knockdown phenocopied SOP's antiproliferative effect with no additivity upon combination. Collectively, this first report demonstrates that SOP restrains pancreatic cancer cell proliferation, with
PTPN1
identified as a key functionally required downstream mediator based on integrative computational and functional evidence. This work offers an integrated strategy for mechanistic exploration and highlights
PTPN1
as a promising therapeutic biomarker and target for pancreatic cancer.