瑞芬太尼对脑胶质瘤细胞恶性生物学行为的影响机制研究OA

Objective To investigate the effects of remifentanil on malignant biological behaviors of glioma cells and its potential mechanism.Methods U87 MG glioma cells were treated with remifentanil at concentrations of 0,0.5,1.0,2.0,4.0,and 8.0 mg/mL.Cell viability was assessed by CCK-8 assay,and IC50 was calculated.U87 MG cells were divided into the Control group,the Remifentanil group,the Remifentanil+Jagged-1/Notch signaling pathway activator group(the Remifentanil+Jagged-1 group),the Jagged-1/Notch signaling pathway inhibitor group(the DAPT group),and the Remifentanil+Jagged-1/Notch signaling pathway inhibitor group(the Remifentanil+DAPT group).Cell colony formation assay was used to detect cell proliferation ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the expression levels of proteins related to cell proliferation,apoptosis,epithelial-mesenchymal transition(EMT),and the Jagged-1/Notch signaling pathway.A nude mouse xenograft tumor model was established to evaluate the effects of remifentanil on tumor growth and the expression levels of proteins related to Jagged-1/Notch signaling pathway.Immunohistochemistry was used to detect the expression levels of proliferation,apoptosis,and EMT-related proteins in tumor tissues.Results Compared with the Control group,the number of cell colonies and the expression levels of Ki67,PCNA,Snail,N-cadherin,Vimentin,Jagged-1,Notch1 and Hes1 proteins in both the Remifentanil group and the DAPT group were decreased(P<0.05),while the apoptosis rate and the expression levels of Bax and C-caspase-3 proteins were increased(P<0.05).Compared with the Remifentanil group,the number of cell colonies and the expression levels of Ki67,PCNA,Snail,N-cadherin,Vimentin,Jagged-1,Notch1 and Hes1 proteins in the Remifentanil+Jagged-1 group were increased(P<0.05),while the apoptosis rate and the expression levels of Bax and C-caspase-3 proteins were decreased(P<0.05).Compared with the Remifentanil group and the DAPT group,the number of cell colonies and the expression levels of Ki67,PCNA,Snail,N-cadherin,Vimentin,Jagged-1,Notch1 and Hes1 proteins in the Remifentanil+DAPT group were decreased(P<0.05),while the apoptosis rate and the expression levels of Bax and C-caspase-3 proteins were increased(P<0.05).The results of the nude mouse xenograft tumor experiment showed that compared with the NC group,the tumor volume and tumor weight,as well as the expression levels of Jagged-1,Notch1,Hes1,Ki67,PCNA,Snail,N-cadherin and Vimentin in the REM group were decreased(P<0.05),while the expression levels of Bax and C-caspase-3 were increased(P<0.05).Conclusion Remifentanil inhibits the proliferation and EMT and promotes apoptosis of glioma cells,and this effect is associated with the inhibition of Jagged-1/Notch signaling pathway.