负载胃泌素-生存素-热休克蛋白融合蛋白树突状细胞在体内外抗肿瘤活性研究

Study on anti-tumor activity of gastrin-survival protein-heat shock protein fusion protein dendritic cells in vivo and in vitro

目的研究胃泌素-生存素-热休克蛋白(Gas-Sur-Hsp70L1)融合蛋白在体外对人树突状细胞的活化作用以及在小鼠体内抑制肿瘤细胞生长的作用。方法鉴定Gas-Sur-Hsp70L1融合蛋白并激活未成熟树突状细胞,对树突状细胞在体外活化作用进行观察;并分析Gas-Sur-Hsp70L1融合蛋白抑制小鼠肿瘤细胞生长的体内机制。结果生存素的特异性在Gas-Sur-Hsp70L1融合蛋白中同样存在。Gas-Sur-Hsp70L1融合蛋白使树突状细胞表面分子CD86的表达上调,其上调率为52.93%。动物体内实验显示,肿瘤细胞在应用Gas-Sur-Hsp70L1融合蛋白处理后明显受到抑制,10μg Gas-Sur-Hsp70L1融合蛋白组肿瘤体积与阴性对照组和空白对照组比较差异均有统计学意义(P均<0.05),其抑瘤率为61.01%,最为明显。结论Gas-Sur-Hsp70L1融合蛋白可以活化体外树突状细胞,能有效抑制小鼠体内肿瘤细胞生长,Gas-Sur-Hsp70L1融合蛋白可能具有抗肿瘤作用。

Objective To study the effect of gastrin-survival protein-heat shock protein(Gas-Sur-Hsp70L1)fusion protein on activation of human dendritic cells in vitro and inhibition of growth of survival protein-positive tumor cells in mice.Methods The Gas-Sur-Hsp70L1 fusion protein was identified and the activation of immature dendritic cells was observed.The activation of Gas-Sur-Hsp70L1 fusion protein on dendritic cells in vitro was observed.The mechanism in vivo of fusion protein inhibiting tumor cell growth was observed in mice.Results The specificity of survival protein existed in the Gas-Sur-Hsp70L1 fusion protein too.The expression of CD86 on the surface of dendritic cells was up-regulated by gas-sur-Hsp70L1 fusion protein,with an up-regulated rate of 52.93%.In vivo experiments on animals showed that tumor cells were significantly inhibited after the application of Gas-Sur-Hsp70L1 fusion protein,and the tumor volume inhibition rate of the 10μg Gas-Sur-Hsp70L1 fusion protein treatment group was 61.01%,and the difference was statistically significant compared with the negative control group and the blank control group(P<0.05).Conclusion Gas-Sur-Hsp70L1 fusion protein can activate dendritic cells in vitro and effectively inhibit tumor cell growth in mice.Gas-Sur-Hsp70L1 fusion protein may have anti-tumor therapeutic effects.