Objective:To investigate the effect of glioma cell-derived apoptotic extracellular vesicles(apoEVs)on glioma tumorigen-esis and temozolomide(TMZ)resistance and its mechanism.Methods:The extracted apoEVs were characterized using nanoparticle tracking analysis and transmission electron microscopy,and Western blot,flow cytometry,CCK-8 assay,colony formation assay,and Transwell assay were used to investigate the effect of apoEVs on cell proliferation,migration,invasion,and apoptosis.Results:ApoEVs promoted TMZ resistance in glioma cells,significantly increased the half-maximal inhibitory concentration of TMZ(t=9.326,P=0.001),and inhibited cell apoptosis,and this effect could be reversed by the exosome inhibitor GW4869.ApoEVs also promoted the migration and invasion of glioma cells,increased the expression of vimentin and Twist proteins(t=8.762,P=0.002;t=7.941,P=0.004),and inhibited the expression of cleaved caspase-3(t=9.217,P=0.002).Further studies showed that apoEVs affected TMZ resistance of glioma cells by regulating the LncRNA-XIST/miR-29c/O6-methylguanine-DNA methyltransferase(MGMT)axis.Silencing of LncRNA-XIST could reduce the expression of MGMT and increase the expression of miR-29c,thereby enhancing the sensitivity to TMZ and inhibiting cell migration and invasion.Conclusion:Glioma cell-derived apoEVs promote the malignant progression and temo-zolomide resistance of glioma by delivering LncRNA-XIST to regulate the miR-29c/MGMT axis.