Background: Vascular endothelial growth factor (VEGF) is highly
expressed in many types of tumors, including pancreatic cancer. Tumor cellderived
VEGF promotes angiogenesis and tumor progression. However, the
role of VEGF in glucose metabolism remains unclear.
Objective: We investigated the role and the underlying mechanism of VEGF in the glucose metabolism of
pancreatic cancer cells.
Method: Pancreatic cancer cells were stimulated with VEGF165 for 1 or 2 h. The oxygen consumption rates
(OCR) and extracellular acidification rates (ECAR) were measured using the Seahorse XF96 Extracellular Flux
Analyzer. Glycolytic enzymes were detected by quantitative real-time PCR. Neuropilin 1 (NRP1) was silenced
by shRNA in order to investigate its role in VEGF-induced glycolysis. Immunohistochemistry (IHC) was
performed to identify the correlation among VEGF, NRP1 and hypoxia inducible factor 1α (HIF1α) in pancreatic
Results: VEGF stimulation led to a metabolic transition from mitochondrial oxidative phosphorylation to
glycolysis in pancreatic cancer. HIF1α and NRP1 protein levels were both increased after VEGF stimulation.
The down-regulation of NRP1 reduced glycolysis in pancreatic cancer cells. NRP1 and VEGF levels both
correlated with HIF1α expression in pancreatic tumor tissues.
Conclusion: VEGF enhances glycolysis in pancreatic cancer via HIF1α up-regulation. NRP1 plays a key role in