摘要
目的研究GSK3(glycogenkinase3)对胶质瘤分化增殖的影响,并对其进行基因表达相关通路富集分析。方法利用Wnt/β-catenin信号通路激活剂AZD2858,通过抑制GSK3活性的方式激活β-catenin介导的转录。利用GO(gene ontology)和KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库对GSK3抑制前后表达差异显著的基因进行功能类别和通路分析。结果抑制GSK3活性可以引起P53、Wnt等多条信号通路的协同作用,并且通过正向调控细胞死亡相关功能基因Caspase 3、FAS、p21,负向调控细胞周期和细胞分裂相关功能基因Cyclin A、Cyclin B、VEGF、Survivin,最终抑制人脑恶性胶质瘤U87的增殖。结论利用小分子化合物AZD2858抑制GSK3活性可激活人脑恶性胶质瘤中的Wnt/β-catenin信号通路,对胶质瘤细胞增殖起到抑制作用。
Objective To study the effect of glycogenkinase3（GSK3） on the proliferation of human glioma and analyze the enrichment of its gene expression profile. AZD2858, the activator of Wnt/Methods β-catenin signaling pathway, was used to activate the β-catenin-mediated transcription by inhibiting the activity of GSK3. The GO（gene ontology） and KEGG（Kyoto Encyclopedia of Genes and Genomes） database were used to analyze the functional category and pathways on the genes with significant difference in the expression before and after the inhibition of GSK3. Results The inhibition of the activity of GSK3 may cause the synergistic effect of multiple signaling pathways including P53 and Wnt. The proliferation of human brain glioma U87 was finally inhibited through positive regulation of the functional genes related to cell death including Caspase 3, FAS and p21, and negative regulation of the functional genes related to cell cycle and cell division including Cyclin A, Cyclin B, VEGF and Survivin. Conclusion Using the small molecule compound AZD2858 to inhibit the activity of GSK3 can activate the Wnt/β-catenin signaling pathway of human brain glioma and inhibit the proliferation of glioma cells.
作者
岑学程
高力扬
陈兵
杨帆
龙霄翱
顾雪锋
李锦宏
CEN Xue-cheng;GAO Ll-yang;CHEN Bing;YANG Fan;LONG Xiao-ao;GU Xue-feng;LI Jin-hong(Department of Neurosurgery;Stem Cell Research and Transformation Center,the Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China)
出处
《广东医科大学学报》
2018年第1期36-39,共4页
Journal of Guangdong Medical University
基金
广东省自然科学基金(No.2016A030313680)
广东省卫生厅项目(No.A2015483)
