重组腺病毒介导Hsp70基因表达对胰腺癌荷瘤小鼠的免疫功能影响

The immune function effect of recombinant adenovirus-mediated Hsp70 gene expression on tumor-bearing mice of pancreatic cancer

目的观察重组腺病毒介导热休克蛋白质70(Hsp70)基因表达对胰腺癌荷瘤小鼠的治疗作用及其对免疫功能的影响。方法建立胰腺癌荷瘤小鼠动物模型,随机分为荷瘤组、对照组和治疗组,对比不同时间点三组肿瘤大小,评价抑瘤效果。通过Western blot检测移植瘤组织Hsp70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IL-2、INF-γ、IL-4、IL10的含量。结果与荷瘤组和对照组相比,治疗组肿瘤生长受到明显抑制(P<0.05或P<0.01),脾单核细胞中CD4+、CD8+细胞比例明显增加(P<0.01)。治疗组血清中细胞因子IL-2、INF-γ含量较荷瘤组和对照组明显增加(P<0.01),IL-10含量则明显减少(P<0.01)。结论重组腺病毒介导的Hsp70基因表达对荷瘤小鼠胰腺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 recombinant adenovirus-mediated heat shock protein 70（Hsp70） gene expression on tumor-bearing mice of pancreatic cancer,and to investigate its influence on immune function. Methods Mouse tumor bearing models of pancreatic cancer were established and were randomly divided into tumor-bearing group,control group and treat ment group. Antitumor effect was evaluated by comparing tumor size of the three groups at different time points. HspT0 protein ex pression in transplanted tumor tissue was analyzed by Western blot. ELISA method was used to detect cytokines IL-2, INF-r,IL-4 and IL-10 level in peripheral blood. The proportion of CD4＋ and CD8＋ cells of spleen mononuclear cells were evaluated by flow ey- tometry. Results Compared with the tumor-bearing group and the control group,tumor growth in the treatment group was signifi- cantly inhibited（P〈0.05 or P〈0.01） CD4＋ and CD8＋ cells ratio in the treatment group was significantly higher than those in the tumor-bearing group and the control group（P〈0.01）. Serum cytokines IL-2, INF-rcontent in the treatment group increased signif icantly（P%0.01） and IL-10 content reduced significantly（P〈0.01）. Conclusion Hsp70 gene expression mediated by recombinant adenovirus can inhibit tumor growth in mouse xenograft models of pancreatic cancer and its mechanism is related to stimulating the immune system.