AKT是骨髓增殖性肿瘤的治疗靶点  

AKT Is A Therapeutic Target in Myeloproliferative Neoplasms

作　　者：余金[1] 黄赞[2] 范静怡[1] 

机构地区：[1]武汉大学中南医院儿科,湖北武汉430071 [2]武汉大学生命科学学院,湖北武汉430072

出　　处：《中国实验血液学杂志》2017年第4期1105-1112,共8页Journal of Experimental Hematology

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。Objective： To study the therapeutic effect of AKT inhibitor on the myeloproliferative neoplasms（ MPN）and its significanse. Methods： The MPL W515 L expression was induced by retroviral infection to construct the MPN cell model. The constitutive activation of the signal pathway was detected by Western blot assay. Cells were treated by AKT inhibitor and the proliferation of MPN cells were detected by cell counting method and clone formation unit test. Annexin V staining was used to detect cell apoptosis,and the cell cycle was detected by BrdU method. The animal survival experiment was performed to analyze the effect of AKT inhibitor on the survival rate of MPN mouse model. Results：The overexpression of MPL W515 L could significantly activate PI3K/AKT,JAK/STAT and other signaling pathways.Blocking these signal pathways could inhibit the proliferation and promote the apoptosis of MPN cell model. Among them,the PI3K/AKT inhibitor had the most significant effect,and the proportion of G1 ME cells in the mitotic phase S decreased,while the proportion of G_1/G_0 phase increased,the cell cycle arrest function was shown. At the same time,in the blood samples of patients with MPN,blocking PI3K/AKT could also inhibit the colony forming units of bone marrow progenitor cells,and significantly increased the survival rate of animal model. Conclusion： AKT is a target for the treatment of bone marrow proliferative tumors

关 键 词：细胞生物学 PI3K/AKT AKT抑制剂 骨髓增殖性肿瘤 

分 类 号：R551.3[医药卫生—血液循环系统疾病]