缺氧诱导的间充质干细胞外泌体对胃癌细胞生长和转移的影响及机制  

Effect and mechanism of hypoxia induced mesenchymal stem cell exosomes in regulating the growth and metastasis of gastric cancer cells

作　　者：杜雄[1] 李延新[1] 段小瑞 康婷[2] DU Xiong;LI Yanxin;DUAN Xiaorui;KANG Ting(Department of Pathology,Affiliated Hospital of Yan′an University,Yan′an,Shaanxi 716000,China;Department of Oncology,Affiliated Hospital of Yan′an University,Yan′an,Shaanxi 716000,China)

机构地区：[1]延安大学附属医院病理科,陕西延安716000 [2]延安大学附属医院肿瘤科,陕西延安716000

出　　处：《国际检验医学杂志》2021年第22期2724-2728,2734,共6页International Journal of Laboratory Medicine

基　　金：陕西省重点研发计划项目(2019SF-132)。

摘　　要：目的探讨缺氧条件下间充质干细胞外泌体对胃癌细胞生长和转移的影响及机制。方法在正常和缺氧条件下培养人骨髓间充质干细胞,差速离心法收集细胞培养上清液中的外泌体,透射电镜和蛋白质印迹法(Western blot)鉴定外泌体,将胃癌细胞MGC-803分别与磷酸盐缓冲液(PBS)、正常间充质干细胞外泌体(Nom-exo)、缺氧诱导的间充质干细胞外泌体(Hypo-exo)孵育,CCK8检测细胞增殖能力、流式细胞术检测细胞凋亡、Transwell小室法检测细胞迁移和侵袭能力,Western blot检测CD44、c-myc、G1/S-特异性周期蛋白-D1(Cyclin D1)、磷酸化的β-连环素(p-β-catenin)、β-连环素(β-catenin)表达水平。结果相比于PBS组,Nom-exo和Hypo-exo组MGC-803细胞增殖能力、迁移和侵袭能力显著增加(P<0.05)、凋亡水平显著下降(P<0.05),Wnt/β-catenin信号通路显著激活(P<0.05);相比于Nom-exo组,Hypo-exo组MGC-803细胞增殖能力、迁移和侵袭能力显著增加(P<0.05)、凋亡水平显著下降(P<0.05),Wnt/β-catenin信号通路亦显著激活(P<0.05)。结论缺氧条件下,间充质干细胞外泌体能够显著促进胃癌细胞的生长和转移,其机制为促进Wnt/β-catenin信号通路的激活。Objective To investigate the effect and mechanism of mesenchymal stem cell exosomes on the growth and metastasis of gastric cancer cells under hypoxic conditions.Methods Human bone marrow mesenchymal stem cells were cultured under normal and hypoxic conditions.The exosomes in the cell culture supernatant were collected by differential centrifugation.Exosomes were identified by transmission electron microscopy and Western blot.The gastric cancer cells MGC-803 were separated from phosphate buffered saline(PBS),normal mesenchymal stem cell exosomes(Nom-exo),hypoxia-induced mesenchymal stem cell exosomes(Hypo-exo)incubation,CCK8 was used to detect cell proliferation and flow cytometry was used to detect apoptosis,Transwell cell methods were used to detect the cell migration and invasion ability.Western blot was used to detect the expression levels of CD44,c-myc,Cyclin D1,p-β-catenin andβ-catenin.Results Compared with PBS group,the proliferation ability,migration and invasion ability of MGC-803 cells in Nom-exo and Hypo-exo groups were significantly increased(P<0.05),the apoptosis level was significantly decreased(P<0.05),and Wnt/β-catenin signaling pathway was significantly activated(P<0.05).Compared with Nom-exo group,the proliferation ability,migration and invasion ability of MGC-803 cells in Hypo-exo groups were significantly increased(P<0.05),the apoptosis level was significantly decreased(P<0.05),and Wnt/β-catenin signaling pathway was significantly activated(P<0.05).Conclusion In hypoxic conditions,mesenchymal stem cell exosomes can significantly promote the growth and metastasis of gastric cancer cells,the mechanism is to promote the activation of Wnt/β-catenin signaling pathway.

关 键 词：缺氧 间充质干细胞 外泌体 胃癌 生长 转移 

分 类 号：R735.2[医药卫生—肿瘤]