胶质瘤干细胞外泌体通过PI3K/Akt信号通路促进胶质瘤U87细胞侵袭、迁移

目的 探讨胶质瘤干细胞（GSCs）外泌体（exo）对胶质瘤U87细胞侵袭、迁移的影响。方法 取对数生长期U87细胞，应用干细胞培养液分离、培养胶质瘤U87细胞中GSCs并提取、鉴定GSCs-exo。取对数生长期U87细胞随机分为4组:对照组和高、中、低GSCs-exo浓度组（分别加入20、40、80 μg/ml的GSCs-exo）。Transwell实验检测U87细胞侵袭能力，划痕实验检测U87细胞迁移能力，免疫印记法检测U87细胞磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）、L1CAM的表达水平。结果 成功分离GSCs并获得GSCs-exo。GSCs-exo组U87侵袭细胞数、细胞迁移率明显高于对照组（P<0.05），L1CAM、PI3K及p-AKt/Akt表达水平明显高于对照组（P<0.05），而且均呈浓度依赖性（P<0.05）。结论 GSCs-exo可促进胶质瘤侵袭与转移，其机制可能与上调L1CAM、PI3K表达，促进Akt磷酸化有关。

Glioma stem cell-derived exosomes promote glioma U87 cell invasion and migration through PI3K/Akt signaling pathway

Objective To study the effect of glioma stem cell-derived exosoms(GSCs-exo)on the cell invasion and migration of cultured human glioma U87 cells.Methods GSCs were isolated from human glioma U87 cells and cultured using stem cell culture media.Then GSCs-exos were extracted and identified from the cell culture supernatant of the GSCs culture media.U87 cells were cultured and randomly divided into four groups,i.e.;control group,and high,medium and low GSCs-exo concentration groups(adding 20,40,80μg/ml GSCs-exo into the cluture media,respectively).The invasion ability of U87 cells was detected by Transwell experiment,the migration ability of U87 cells was detected by the scratch experiment,and the expression levels of phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)and L1CAM in U87 cells were detected by the western blotting.Results GSCs and GSCs-exo were successfully separated and identified.The number of U87 invasion cells and cell migration rate in the GSCs-exo groups were significantly higher than those in the control group(P<0.05),and the expression levels of L1CAM,PI3K and p-AKt/Akt were significantly higher than those in the control group(P<0.05),and all the effects of GSCs-exo were concentration dependent(P<0.05).Conclusions GSCs-exo can promote the invasion and migration of glioma cells,and its mechanism may be related to the up-regulation of L1CAM and PI3K/Akt.