四代聚酰胺-胺型枝状聚合物纳米粒介导HSP90基因表达对结肠癌荷瘤小鼠的免疫功能影响

The immunefunction effect of PAMAM nanoparticles mediated HSP90 gene expression on tumor bearing mice of Colon cancer

目的观察四代聚酰胺-胺型枝状聚合物纳米粒介导热休克蛋白质90(HSP90)基因表达对结肠癌荷瘤小鼠的治疗作用及其对免疫功能的影响。方法建立结肠癌荷瘤小鼠动物模型,随机分为空白组、转染空载体对照组和转染HSP90基因表达组,对比不同时点三组肿瘤的大小,评价抑瘤效果。通过Westernblot检测移植瘤组织HSP90蛋白表达,流式细胞仪检测脾单核细胞中CD4+、CD8+细胞比例,ELISA检测血清中细胞因子IL2、INFγ、IL8、IL10的含量。结果与空白组和转染空载体组相比,转染HSP90基因表达组肿瘤生长受到明显抑制(P<0.05),脾单核细胞中CD4+、CD8+细胞比例明显增加(P<0.05)。结论治疗组血清中细胞因子IL2和INFγ含量较荷瘤组和对照组明显增加(P<0.05),IL10含量基因表达对荷瘤小鼠结肠癌动物模型的肿瘤生长具有抑制作用,其机制与激发免疫系统功能有关。

【Objective】To observe the therapeutic effect of P0AMAM nanoparticles mediated HSP90 gene expression bearing mice of Colon cancer,and to invsetigate its influence on immunefunction.【Methods】Mouse tumor bearing models of colon cancer were established and were randomly divided into tumor bearing group,transfected with blank vector group,and transfected with HSP90 gene expression group.Antitumor effect was evaluated by compareing tumor size of the three groups at different time points.HSP90 protein expression in transplanted tumor tissue was analyzed by Westernblot.ELISA method was used to detect cytokines IL2,INFγ,IL8 and IL10 level in peripheralblood.The proportion of CD4＋ and CD8＋ cells of spleen mononuclear cells were evaluated by flowcytometry.【Results】Compared with the tumor bearing group and the control proup,tumor growth in the treatment group was significantly inhibited（P〈 0.05）.CD4＋ and CD8＋ cells ratio in the treatment group was significantly higher than those in the tumor bearing group,transfected with blank vector group（P〈 0.05）.Serum cytokines IL2,INFγ,content in the transfected with HSP90 gene expression group increased significantly（P〈 0.05） and IL10 content reduced significantly（P〈 0.05）.【Conclusions】HSP90 gene expression mediated by PAMAM nanoparticles can inhibit tumor growth in mouse xenograft moedls of Colon cancer and its mechanism is related to stimulating the immunesystem.