GDC-0032抑制U251胶质瘤细胞活力并诱导DNA损伤

发布时间：2018-06-10 05:55

本文选题：GDC- + 胶质瘤　；参考：《中国病理生理杂志》2017年10期

【摘要】：目的:探讨磷脂酰肌醇3-激酶(PI3K)抑制剂GDC-0032对人胶质瘤U251细胞活力、细胞周期和DNA损伤的影响。方法:GDC-0032处理U251细胞,MTT实验检测细胞活力;流式细胞术分析GDC-0032对细胞周期的影响;Western blot检测细胞内蛋白表达的变化;免疫荧光检测组蛋白γ-H2AX在细胞内的表达与分布。结果:GDC-0032剂量依赖性地抑制U251细胞活力;U251细胞经GDC-0032作用后,处于G1期的细胞数量明显增多,同时p27的表达水平增加,而细胞分裂周期蛋白2(Cdc2)的表达则受到抑制;在GDC-0032作用的细胞中,γ-H2AX焦点的生成和表达水平明显升高;另外,GDC-0032上调胶质瘤细胞中丝裂原活化蛋白激酶家族成员细胞外信号调节激酶(ERK)和c-Jun氨基末端激酶(JNK)的磷酸化水平,而survivin的表达则受到抑制。结论:GDC-0032能够通过抑制细胞活力和阻滞细胞于G1期而抑制U251细胞的增殖,并且诱导胶质瘤细胞发生DNA损伤;GDC-0032的抑癌活性与其调控ERK和JNK的活性及下调survivin的表达相关。
[Abstract]:Aim: to investigate the effects of phosphatidylinositol 3-kinase (PI3K) inhibitor GDC-0032 on the viability, cell cycle and DNA damage of human glioma U251 cells. Methods the cell viability was detected by MTT assay, the effect of GDC-0032 on cell cycle was analyzed by flow cytometry, and the expression and distribution of histone 纬 -H2AX in U251 cells were detected by blot and immunofluorescence. Results after treated with GDC-0032, the number of U251 cells in G1 phase was significantly increased, and the expression level of p27 was increased in a dose-dependent manner, while the expression of cyclin 2 CDc2) was inhibited in a dose-dependent manner. In addition, GDC-0032 up-regulated the phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun amino-terminal kinase (JNKK) in glioma cells. The expression of survivin was inhibited. Conclusion the proliferation of U251 cells can be inhibited by inhibiting cell viability and blocking cell proliferation in G1 phase. The inhibitory activity of glioma cells induced by GDC-0032 is related to its regulation of ERK and JNK activity and down-regulation of survivin expression.
【作者单位】：泰山医学院护理学院;郑州大学第一附属医院;泰山医学院生命科学研究中心;泰山医学院第二临床医学院;
【基金】：山东省自然科学基金资助项目(No.ZR2014HL107)
【分类号】：R739.4

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