AKT是骨髓增殖性肿瘤的治疗靶点

发布时间：2018-09-09 20:13

【摘要】：目的:研究AKT抑制剂对骨髓增殖性肿瘤(MPN)的治疗效果及其意义。方法:逆转录病毒感染介导MPL W515L过表达,构建M PN细胞模型。蛋白印迹实验检测信号通路的组成型活化。AKT信号通路抑制剂处理细胞并行细胞计数法,应用克隆形成单位试验检测MPN细胞的增殖。Annexin V染色检测细胞凋亡,Brd U法检测细胞周期。应用动物生存实验分析AKT信号通路抑制剂对MPN小鼠模型存活率的影响。结果:MPL W515L过表达可以显著活化PI3K/AKT、JAK/STAT等信号通路。阻滞上述信号通路能够抑制MPN细胞模型的增殖、促进凋亡,其中以PI3K/AKT抑制剂效果最显著,并使G1ME细胞处于有丝分裂S期的比例减少、处于G_1/G_0期的比例升高,显示出细胞周期阻滞功能。同时,在MPN病人的血液样本中,阻滞PI3K/AKT也能够抑制骨髓祖细胞的克隆形成单位,并显著增加动物模型的存活率。结论:AKT是骨髓增殖性肿瘤的治疗靶点。
[Abstract]:Objective: to study the therapeutic effect of AKT inhibitor on bone marrow proliferative tumor (MPN) and its significance. Methods: M PN cell model was constructed by overexpression of MPL W515L mediated by retrovirus infection. Western blotting assay was used to detect the compositional activation of signal pathway. AKT signal pathway inhibitor was used to treat cells and cell counting was performed. The proliferation of MPN cells was detected by clone forming unit assay. Annexin V staining was used to detect cell apoptosis and cell cycle was detected by BrdU method. The effect of AKT signaling pathway inhibitor on survival rate of MPN mice was analyzed by animal survival experiment. Results the overexpression of W515L could significantly activate the signal pathway such as PI3K/AKT,JAK/STAT. Blocking the above signaling pathway could inhibit the proliferation of MPN cell model and promote apoptosis. The effect of PI3K/AKT inhibitor was the most significant, and the proportion of G1ME cells in mitotic S phase was decreased, and the proportion in G_1/G_0 phase was increased. Cell cycle arrest was demonstrated. At the same time, blocking PI3K/AKT in blood samples of MPN patients also inhibited the colony forming units of bone marrow progenitor cells and significantly increased the survival rate of animal models. Conclusion\
【作者单位】：武汉大学中南医院儿科;武汉大学生命科学学院;
【分类号】：R733.3

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