Effects of sirolimus on cell proliferation and apoptosis of vascular endothelial cells of venous malformation induced by TIE2-L914F mutation and its mechanism in vitro / 安徽医科大学学报

ABSTRACT

Objective@#The purpose of this study was to investigate the effects of sirolimus ( SIR) on proliferation and apoptosis of vascular endothelial cells of venous malformation ( VM) caused by mutations in TIE2-L914F and its potential molecular mechanism．@*Methods @#The expression of TEK receptor tyrosine kinase ( TIE2 ) in human umbilical vein endothelial cell (HUVEC) was interfered to construct vascular endothelial cells of VM model (TIE2-L914F group) ．Subsequently part of vascular endothelial cells of VM was exposed to 1 000 ng / ml SIR for 48 h (TIE2-L914F + SIR group) ，and the proliferation and apoptosis of vascular endothelial cells of VM were detected by MTT and flow cytometry．The mRNA and protein expressions of CXCL1 and CXCR2 were detected by qRT-PCR and Western blot. @*Results @#Compared with the cells in TIE2-L914F group，the proliferation activity of the cells in TIE2-L914F + SIR group was inhibited，and the apoptosis rate increased (P ＜0. 05) ．The expression of CXCL1 increased in TIE2-L914F cells but decreased after SIR treatment (P＜0. 05) ．Compared with TIE2-L914F + pcDNA3．1 group，the cell proliferation activity increased but apoptosis rate decreased in TIE2-L914F + pcDNA-CXCL1 group．Compared with TIE2-L914F + pcDNA-CXCL1 group，cell proliferation activity was inhibited but apoptosis rate increased in TIE2-L914F + pcDNA-CXCL1 + SIR Group (P＜0. 05) ．In addition，compared with TIE2-L914F group，CXCR2 expression decreased in TIE2-L914F + SIR group(P＜0. 05)．@*Conclusion @#SIR inhibits VM cell proliferation，induces cell apoptosis of vascular endothelial cells of VM，and inhibits the expression of CXCL1 / CXCR2.