木犀草素通过GSK-3β/β-catenin通路抑制胶质母细胞瘤细胞侵袭、迁移及上皮间质转化  

Luteolin inhibits invasion,migration,and epithelial-mesenchymal transition of glioblastoma through GSK-3β/β-catenin pathway

作　　者：蒋航 犹秋香 陈波 曾雪 王龙 张云东 JIANG Hang;YOU Qiuxiang;CHEN Bo;ZENG Xue;WANG Long;ZHANG Yundong(Center of Neuropathies,the Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China;College of Pharmacy,Chongqing Medical University,Chongqing 400016,China;Department of Neurosurgery,the First Affiliated Hospital,Army Medical University,Chongqing 400038,China)

机构地区：[1]重庆医科大学附属第三医院神经疾病中心,重庆401120 [2]重庆医科大学药学院,重庆400016 [3]陆军军医大学第一附属医院神经外科,重庆400038

出　　处：《现代肿瘤医学》2023年第22期4115-4122,共8页Journal of Modern Oncology

基　　金：重庆医科大学附属第三医院科研孵化项目(编号:KY19026)。

摘　　要：目的:研究木犀草素对人胶质瘤U87及U251细胞侵袭、迁移能力的影响及其机制。方法:体外培养胶质瘤U87及U251细胞系,将对数生长期细胞随机分为对照组及木犀草素处理组,利用CCK-8实验检测细胞活力,划痕实验及Transwell实验检测胶质瘤细胞迁移侵袭能力,Western blot实验及免疫荧光实验检测木犀草素对胶质瘤细胞上皮间质转化相关蛋白及GSK-3β/β-catenin信号通路的影响;使用GSK-3β/β-catenin信号通路抑制剂(G?6983)或激动剂(LiCl)处理U87及U251细胞验证木犀草素对U87及U251细胞相关蛋白表达及侵袭迁移能力的影响。裸鼠成瘤实验探究木犀草素对裸鼠体内瘤体的瘤重、瘤体积的影响。结果:木犀草素以时间浓度依赖性抑制胶质瘤U87及U251细胞活性。划痕实验及Transwell实验显示,木犀草素处理组较对照组细胞侵袭迁移能力降低(P<0.05)。木犀草素处理使胶质瘤细胞由间充质形态向上皮细胞形态转变。与对照组相比,木犀草素组N-cadherin、Vimentin、β-catenin(胞浆、胞核)、p-GSK-3β(Ser9)等蛋白水平降低,而E-cadherin蛋白水平上升(P<0.05)。GO6983处理可加强木犀草素对上皮间质转化及GSK-3β/β-catenin信号通路的影响;LiCl处理可逆转木犀草素对上皮间质转化、GSK-3β/β-catenin信号通路及侵袭迁移能力的影响。体内实验显示,木犀草素治疗组瘤体体积、瘤体质量较对照组降低(P<0.05)。结论:木犀草素可以抑制胶质瘤U87及U251细胞侵袭和迁移,其机制可能是通过调节GSK-3β/β-catenin信号通路而抑制EMT过程。Objective:To investigate the effect of luteolin on the invasion and metastasis ability of human glioma U87 and U251 cell lines and its mechanism.Method:Human glioma U87 and U251 cells were cultured in vitro and randomly divided into control group and luteolin group in the logarithmic growth phase.Cell viability,migration and invasiveness of glioma cells were detected by CCK-8 test,scratch test and Transwell test.Western blot test and immunofluorescence test were used to detect the effects of luteolin on epithelial-mesenchymal transition(EMT) related protein of glioblastoma and GSK-3β/β-catenin signaling pathway.The effects of luteolin on the expression of proteins,migration and invasiveness were validated by treating U87 and U251 cells with a GSK-3β/β-catenin signaling pathway inhibitor(GO6983) or agonist(LiCl).The effects of luteolin on tumor weight and volume in vivo were observed by the tumorigenesis experiment in nude mice.Results:The results showed that luteolin inhibited the activity of glioma U87 and U251 cells in a concentration-dependent manner.The scratch test and Transwell test showed that the cell invasion and migration ability was reduced in the luteolin treatment group compared to the control group(P<0.05).Luteolin treatment made glioma cells change from mesenchymal morphology to epithelial morphology.Compared with the control group,the luteolin treatment could down-regulate the level of N-cadherin,Vimentin and β-catenin(cytoplasm,nucleus),p-GSK-3β(Ser9),while up-regulate the levels of E-cadherin protein(P<0.05).G?6983 can enhance the effect of luteolin on EMT and GSK-3β/β-catenin signaling pathway.LiCl can reverse the influence of luteolin on EMT,GSK-3β/β-catenin signaling pathway,invasion and migration ability of glioma.In vivo experiments showed that compared with the control group,the luteolin treatment could reduce tumor volume and mass(P<0.05).Conclusion:Luteolin can inhibit the invasion and migration of glioma U87 and U251 cells.Its mechanism may be related to the regulation of GSK-

关 键 词：胶质母细胞瘤 木犀草素 侵袭迁移 上皮间质转化 GSK-3β/β-catenin信号通路 

分 类 号：R739.4[医药卫生—肿瘤]