摘要
目的研究Yes相关蛋白(YAP)靶向抑制剂维替泊芬(VP)联合放疗对脑胶质瘤细胞增殖与迁移行为的影响及机制。方法对脑胶质瘤细胞分别用放疗、VP、VP联合放疗3种不同的方法进行处理,应用集落形成实验、CCK-8实验检测细胞增殖情况;应用免疫印迹实验探究VP联合放疗增强放疗效果的机制;应用划痕实验检测细胞迁移情况。结果放疗或VP处理均能抑制细胞增殖,放疗联合VP处理的细胞增殖速度受到的抑制效果更为显著;VP联合放疗之后,细胞周期蛋白激酶4(CDK4)和磷酸化Rb(p-Rb)的蛋白表达水平显著低于对照组,细胞周期阻滞,增殖减慢;放疗或VP处理均抑制细胞迁移,放疗联合VP处理后,细胞的迁移能力下降更为显著。结论VP能够明显提高脑胶质瘤的放疗效果;VP联合放疗通过阻断Yes相关蛋白-转录增强结合域(YAP-TEAD)的结合,阻滞细胞周期,从而抑制细胞的增殖。
Objective To study the effect and mechanism of verteporfin(VP),a Yes-associated protein(YAP)targeted inhibitor,combined with radiotherapy on the proliferation and migration behavior of gliomas.Methods After having been treated with radiotherapy,VP or VP combined with radiotherapy,glioma cell proliferation was detected by colony formation assay and CCK-8 assay.The molecular mechanism of VP combined with radiotherapy was explored using Western blotting.The cell migration was detected by wound healing assay.Results Cell proliferation decreased after radiotherapy or VP treatment alone.The inhibition effect of radiotherapy combined with VP treatment on cell proliferation was more significantly.After VP combined with radiotherapy treatment,the protein expression of cyclin-dependent kinase 4(CDK4)and phospho-Rb(p-Rb)significantly decreased.Radiotherapy or VP treatment alone inhibited cell migration.The cell migration capacity decreased more significantly after radiotherapy combined with VP treatment.Conclusions VP can significantly improve the anti-tumor effect of radiotherapy on glioma.VP combined with radiotherapy can block cell cycle and cell proliferation by interfering the interaction of YAP-transcriptional enhanced associate domains(YAP-TEAD).
作者
杨新月
徐静
白雪
陈金灿
张宇
赵敏
王岩
周秀萍
YANG Xinyue;XU Jing;BAI Xue;CHEN Jincan;ZHANG Yu;ZHAO Min;WANG Yan;ZHOU Xiuping(School of Public Health,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;Institute of Nervous System Diseases,Xuzhou Medical University,Xuzhou,Jiangsu 221002;Department of Neurosurgery,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221002)
出处
《徐州医科大学学报》
CAS
2020年第9期635-639,共5页
Journal of Xuzhou Medical University
基金
江苏省高等学校大学生创新创业训练计划省级指导项目(201810313055X)
江苏省普通高校研究生科研创新计划项目(KYCX19_2225)
国家自然科学基金面上项目(81872053,81902526)。
关键词
脑胶质瘤
Yes相关蛋白
维替泊芬
放疗
增殖
glioma
Yes-associated protein
verteporfin
radiotherapy
cell proliferation
