侯晓;李纯璞;郭冬梅;倪梅;陈丽;程雪梅;张开刚;

• 1:山东省泰安市中心医院骨外科

摘要(Abstract)：

[目的]研究Notch-1通道阻断剂γ分泌酶抑制剂(gamma-secretase inhibitor,GSI)在抑制骨肉瘤小鼠模型中肿瘤增长以及其抑制肿瘤血管生成作用,进而探讨Notch-1信号通路在小鼠骨肉瘤模型中的作用及其作用机制。[方法]建立人骨肉瘤荷瘤SCID小鼠模型,将荷瘤成功后小鼠随机分为三组,实验组肿瘤内注射Notch通路阻断药物GSI,对照组注射PBS和DMSO。研究各组小鼠生物学指标、肿瘤增长变化及肿瘤组织检测微血管密度(microvessel density,MVD)的表达情况与差异。[结果]处死小鼠测量瘤体,同对照组相比,GSI治疗组小鼠的生物学指标明显较好,其小鼠的体重、饮食、睡眠、运动情况、精神状态、对刺激的反应及小鼠的皮毛光泽度等优于对照组,其皮下肿瘤体积明显较小,实验组平均体积为(196.3 mm3)较DMSO对照组平均体积(650.3 mm3)及PBS对照组平均体积(694.6 mm3)明显缩小,差别具有统计学意义,P<0.01。实验组及对照组内瘤体切片内血管均见不同程度的CD31表达,其表达于血管内皮细胞内,与对照组相比实验组CD31表达均明显降低,实验组及PBS、DMSO对照组CD31平均秩次分别为4.03、28.9和32.5,P<0.05,差异具有统计学意义。[结论](1)证实GSI可抑制SCID小鼠骨肉瘤动物模型肿瘤的生长;(2)GSI对SCID小鼠骨肉瘤动物模型的治疗作用可通过抑制Notch通路进而干预肿瘤血管形成来实现;(3)应用GSI药物阻断Notch信号通路有望成为骨肉瘤抗肿瘤治疗的新方法。

关键词(KeyWords)： 骨肉瘤;Notch信号转导通路;血管生成;γ-分泌酶抑制剂

Abstract:

Keywords:

基金项目(Foundation): 山东省自然科学基金项目(编号:ZR2012HL38);; 山东省优秀中青年科学家科研奖励基金项目(编号:BS2013SF030)

作者(Author): 侯晓;李纯璞;郭冬梅;倪梅;陈丽;程雪梅;张开刚;

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参考文献(References)：

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