YAP-c-Myc信号通路抑制涉及冬凌草甲素抗神经胶质瘤作用  

Inhibition of YAP-c-Myc signaling pathway involved effect of ORI on anti-glioma

作　　者：王宸 陈爽[1] 马晓娇 校欢 邱红梅[1] WANG Chen;CHEN Shuang;MA Xiao-jiao;XIAO Huan;QIU Hong-mei(Chongqing Key Lab of Biochemistry and Molecular Pharmacology,Dept of Pharmacology,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学药理学教研室,重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国药理学通报》2021年第3期403-409,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31400881);重庆市自然科学基金资助项目(No cstc2017jcyjAX0211);重庆医科大学药学院科研资助项目(No YXY2019SDTR01)。

摘　　要：目的探讨冬凌草甲素对神经胶质瘤U87细胞增殖、迁移和凋亡影响及其作用机制是否涉及抑制YAP-c-Myc信号通路。方法采用MTT法检测冬凌草甲素对U87细胞活力的影响;划痕试验检测细胞迁移能力;流式细胞术检测细胞凋亡率;实时荧光定量PCR检测caspase-3、Bcl-2、Bax、YAP、c-Myc mRNA的表达;Western blot检测caspase-3、Bcl-2、Bax、YAP、p-YAP(Ser127)、c-Myc蛋白的表达。结果冬凌草甲素呈剂量依赖性抑制神经胶质瘤U87细胞增殖(P<0.05)及迁移(P<0.01);流式细胞术分析细胞凋亡率明显增加(P<0.01);caspase-3 mRNA和蛋白表达均增高(P<0.05),Bcl-2/Bax mRNA和蛋白表达均明显降低(P<0.05),YAP、c-Myc的mRNA和蛋白表达均明显降低(P<0.05),p-YAP的蛋白表达增高(P<0.05)。结论冬凌草甲素可促进神经胶质瘤U87细胞增殖、迁移并促进胶质瘤细胞凋亡,其机制可能与抑制YAP信号通路相关。Aim To investigate the effects of oridonin on proliferation,migration and apoptosis of U87 glioma cells and to explore the involvement of the mechanism in the inhibition of Yes-associated protein(YAP)-c-Myc signaling pathway.Methods The effect of oridonin on U87 viability was measured by MTT assay;the migration and invasiveness of cells were measured by transwell assays;the apoptotic rates of cells were assessed by flow cytometry;the caspase-3,Bcl-2,Bax,YAP,c-Myc mRNA expression in U87 glioma cells was detected by real-time quantitative PCR;the caspase-3,Bcl-2,Bax,YAP,p-YAP(Ser127),c-Myc protein expressions were detected by Western blot.Results The proliferation of U87 cells was significantly inhibited by oridonin in a dose-dependent manner(P<0.05),and the ability of cell migration and invasion was weakened(P<0.01),cell apoptosis rate in flow cytometry analysis increased significantly(P<0.01),the protein and mRNA expression of caspase-3 increased(P<0.05),the mRNA and protein expression of Bcl-2/Bax decreased(P<0.05),the mRNA and protein expression of YAP and c-Myc decreased(P<0.05),and the protein expression of p-YAP increased(P<0.05).Conclusions Oridonin can significantly inhibit the proliferation and migration of U87 glioma cells and promote the transformation apoptosis of glioma cells;the mechanism may be related to the inhibition of YAP-c-Myc signaling pathway.

关 键 词：冬凌草甲素 神经胶质瘤U87细胞 增殖 迁移 凋亡 YAP C-MYC 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学]