基于PI3K靶点的小儿血管瘤治疗效应及机制探讨

项目名称： 基于PI3K靶点的小儿血管瘤治疗效应及机制探讨

项目编号： No.81460476

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 俞松

作者单位： 遵义医科大学

项目金额： 47万元

中文摘要： 小儿特殊部位和特殊类型血管瘤的治疗手段多样，但各有其局限性，部分难以达到满意的疗效。前期研究发现：小儿增生期血管瘤中PI3K(p85)、p-Akt蛋白和mRNA表达明显高于消退期；体外培养的血管瘤内皮细胞中，p110及p-Akt蛋白表达水平高时，G0/G1期细胞比例较低，细胞总凋亡率低，而p110及p-Akt蛋白表达水平低时，G0/G1期细胞比例高，细胞总凋亡率高；增殖期mTOR表达高于消退期， p70S6K-α表达低于消退期。本项目拟在原有工作的基础上，以小儿血管瘤裸鼠移植、血管瘤血管内皮细胞体外培养为模型，以PI3K/Akt /mTOR信号转导通路为靶点，观察PI3K 单抑制剂NVP-BEZ235和mTOR 单抑制剂CCI-779对血管瘤增殖期的治疗效应，并通过检测PI3K/Akt /mTOR信号轴中效应分子以探讨血管瘤消长的分子机制，为以PI3K为靶点的临床血管瘤治疗提供实验依据。

中文关键词： 血管瘤；PI3K/Akt；/mTOR信号通路；治疗；儿童

英文摘要： In the hemagioma proliferating phase specimens, the expression rate and strength of p85 and p-Akt were higher than them in the involuting phase specimens. In vitro,the percent of vascular endothelial cell was higher in the G0/G1 phase and the apoptosis rate was higher when p110 and p-Akt protein expression level was lower,and them were lower when p110 and p-Akt protein expression level was higher. The expression of mTOR protein was elevated in hemangioma tissue from infants in priliferation stage in contrast to that in involution stage.While the expression of activated downstream p70S6K-α is higher in involution stage than that in proliferation stage.PI3K/Akt signaling pathway may play an important role in the growth and development of hemangioma. The aim of the current investigation to explore the effect of NVP-BEZ235 and CCI-779 in hemangioma animal model,and in vitro culture of human hemangioma endothelium,thus to discover medicine and cellular factors of negative regulation PI3K for hemangioma treatment.

英文关键词： hemagioma;PI3K/AKT/mTOR signaling pathway;Treatment;Child