巴佛洛霉素A1抑制胶质瘤迁移、侵袭及血管生成拟态的生物机制研究  

Biological mechanism of bafilomycin A1inhibiting glioma migration,invasion and vasculogenic-mimicry

作　　者：陈锋龙[1] 陈金龙[1] 张弋[1] Chen Fenglong;Chen Jinjong;Zhang Yi(Department of Neurosurgery,The Third Hospital of Xiamen,361000,China)

机构地区：[1]厦门市第三医院神经外科,厦门361000

出　　处：《立体定向和功能性神经外科杂志》2022年第2期75-80,共6页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：福建省卫生厅医学创新课题项目(编号:2012-CXB-36)。

摘　　要：目的研究巴佛洛霉素A1(Baflomycin A1,BAF-A1)对胶质瘤细胞增殖、侵袭迁移和血管生成拟态(vasculogenic mimicry,vm)的影响及其作用机制探讨。方法(1)利用巴佛洛霉素A1(10nmol/mL)处理胶质瘤细胞系U87和U251后,检测各组液泡-ATP酶(vacular-ATPases,V-ATPases)活性及培养液PH值,利用CCK-8法检测各组细胞增殖情况。(2)利用三维培养技术和Transwell小室观察各组细胞VM形成状态和侵袭能力。(3)采用western-blot法探究各组细胞中PI3K/AKT的表达水平。结果(1)与对照组相比,使用巴佛洛霉素A1处理后,U87和U251细胞的V-ATPase活性受到抑制(P<0.05);细胞外培养液的PH值升高(P<0.05);细胞的增殖和迁移能力被抑制(P<0.05);血管生成拟态能力减弱(P<0.05)。(2)与对照组相比,使用巴佛洛霉素A1处理后,U87和U251细胞的PI3K、AKT蛋白的表达水平均显著降低(P<0.05)。结论巴佛洛霉素A1通过抑制V-ATPase的活性来改变肿瘤的迁移、侵袭和血管生成拟态,其可能与PI3K/AKT等相关信号通路相关。Objective To study the effect of Baflomycin A1(BAF-A1)on glioma cell proliferation,invasion and migration and vasculogenic mimicry(vm)and its mechanism of action.Methods(1)After glioma cell lines U87and U251were treated with pavlomycin A1(10nmol/ml),the activity of vacuolar ATPase(V-ATPase)and the pH value of culture medium were detected,and the cell proliferation of each group was detected by CCK-8method.(2)Three dimensional culture technique and Transwell chamber were used to observe the VM formation state and invasion ability of cells in each group.(3)Western blot was used to explore the expression level of PI3K/Akt in cells of each group.Results(1)Compared with the control group,the V-ATPase of U87and U251cells after treatment with bafilomycin A1,The activity was inhibited(P<0.05);thePH value of the extracellular culture medium was increased(P<0.05);the proliferation and migration of cells were inhibited(P<0.05);the mimic ability of angiogenesis was weakened(P<0.05).(2)Compared with the control group,the expression levels of PI3Kand AKT proteins in U87and U251cells were significantly decreased after treatment with bafilomycin A1(P<0.05).Conclusion Bafilomycin A1alters tumor migration,invasion and angiogenesis mimicry by inhibiting the activity of V-ATPase,which may be related to PI3K/AKT and other related signaling pathways.

关 键 词：巴佛洛霉素A1 胶质瘤 侵袭 血管生成拟态 

分 类 号：R739.41[医药卫生—肿瘤]