Abstract: 【Abstract】 Objective To investigate the effect of the glucose transporter 1 （Glut-1） inhibitor resveratrol on the activity of infantile hemangioma （IH）-derived endothelial cells （HemEC）. Methods IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR（qPCR） and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells （HUVEC）, respectively. HemEC were cultured in vitro and treated with 0 （control group）, 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 （CCK8） assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration （IC50） was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference-t test. Results Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC （1.793 ± 0.041, 1.959 ± 0.144, respectively） than in HUVEC （0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001）. After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups （F = 1 043.00, P < 0.001）, and was significantly lower in all the resveratrol groups than in the control group （all P < 0.05）. The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group （61 ± 5, 13.01% ± 0.45%, respectively） compared with the control group （150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001）. Conclusion The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.

Key words: Hemangioma, Human umbilical vein endothelial cells, Glucose transporter type 1, Cell proliferation, Apoptosis, Resveratrol