Luteolin reduces glucose uptake and malignant phenotypes in pancreatic ductal adenocarcinoma cells: an integrated bioinformatics and in vitro study.

Pancreatic ductal adenocarcinoma (PDAC) exhibits marked metabolic plasticity, but the effects of luteolin on glucose utilisation in PDAC cells remain unclear. We integrated predicted luteolin targets with bulk and single-cell transcriptomic data, weighted gene co-expression network analysis, machine-learning screening, protein-protein interaction analysis, independent-cohort evaluation, and survival analysis. SLC2A1, MET, and LGALS3 were prioritised as PDAC-associated candidates. In GSE71729, the three-gene expression score was strongly associated with a glycolytic programme, and this association remained robust after removal of overlapping genes from the pathway gene sets. In ASPC-1 and PANC-1 cells, luteolin reduced cell viability, colony formation, migration, invasion, and glucose uptake, accompanied by lower GLUT1, p-MET, and LGALS3 protein signals. Molecular docking and molecular dynamics further supported predicted structural compatibility between luteolin and GLUT1. These findings identify reduced GLUT1 abundance and glucose uptake as prominent metabolic features of the PDAC cellular response to luteolin and provide a basis for further investigation of glucose-dependent PDAC states.