Abstract
Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.