摘要
Objective:To investigate the effect of dexmedetomidine on the malignant biological behavior of glioma cells and its mechanism.Methods:Human glioma cell line A172 was cultured in vitro and treated with different concentrations(50,100,200,400,800 mg/L)of dexmedetomidine.The effect of dexmedetomidine on the proliferation of A172 cells was detected by MTT.Flow cytometry was used to detect the effect of dexmedetomidine on the apoptosis of A172 cells.Transwell chamber assay was used to detect the effect of dexmedetomidine on the migration and invasion of A172 cells.The effects of dexmedetomidine on the expression of miR-760 and HDGF were detected by real-time quantitative PCR(qRT-PCR)and Western blot.Dual luciferase reporter assays were used to examine the effect of miR-760 overexpression on wild-type and mutant HDGF luciferase activities.miR-760 mimics and miR-con were transfected into A172 cells to detect changes in cell proliferation,apoptosis,migration and invasion.Western blot was used to detect the expression of MMP-2,MMP-9,Cleaved caspase-3 and Cleaved PARP protein.Results:Dexmedetomidine significantly reduced the survival rate of glioma cells(P<0.05),decreased the number of migrated cells and the number of invasive cells(P<0.05),and inhibited the expression of HDGF,MMP-2 and MMP-9(P<0.05).However,it could increase the apoptosis rate(P<0.05)and promote the expression of miR-760,Cleaved caspase-3 and Cleaved PARP(P<0.05).The effect was obvious when the concentration reaches 800 mg/L.Luciferase reporter gene results confirmed that miR-760 can inhibit the luciferase activity of the 3'-UTR region of HDGF(P<0.05).After transfection of miR-760 mimics,cell viability was significantly lower than that of miR-con group(P<0.05),and the number of migrated cells and invasive cells were significantly decreased(P<0.05),and the expression levels of MMP-2 and MMP-9 were significantly decreased(P<0.05),but the apoptosis rate was significantly increased(P<0.05),and the expression levels of Cleaved caspase-3 and Cleaved PARP were significantly increased(P<0.05).Interference with the expression of miR-760 reversed the effect of dexmedetomidine on the biological behavior of glioma cells.Conclusion:Dexmedetomidine attenuates the proliferation,migration and invasion of glioma cells through miR-760/HDGF and promotes apoptosis.
基金
Hainan provincial commission of health and family planning(No.1601320212A2001)
