甲胎蛋白单抗修饰的载核心蛋白聚糖基因聚乳酸-羟基乙酸靶向纳米粒在H22荷瘤小鼠体内诱导的自噬作用

Induction of autophay by alpha fetal protein monoclonal antibody modified poly(lactic-co-glycolic acid)nanoparticles carrying recombinant human decorin gene in mice bearing H22 cells

目的探讨甲胎蛋白(alpha fetal protein,AFP)单抗修饰的载核心蛋白聚糖(decorin,DCN)基因聚乳酸-羟基乙酸[poly(lactic-co-glycolic acid),PLGA]靶向纳米粒对小鼠肝癌移植瘤生长的影响及与自噬的关系。方法建立小鼠肝癌移植瘤模型,将AFP单抗修饰的纳米粒AFPmAb-PLGA-rhDCN注入肿瘤中央及基底部,并以非特异Ig G-PLGArhDCN纳米粒、PLGA-空质粒及PBS缓冲液作为对照组。测量肿瘤体积及瘤重,免疫组化及Western blot法检测肿瘤组织中自噬相关基因Beclin1蛋白含量的变化。结果与3个对照组相比,AFPmAb-PLGA-rhDCN纳米粒组小鼠肿瘤生长缓慢,肿瘤体积和瘤重均明显减小(P<0.05),肿瘤组织中Beclin1蛋白的表达均明显降低(P<0.05)。结论AFP单抗修饰的载DCN基因纳米粒可抑制小鼠肝癌移植瘤的生长,其机制可能与抑制肿瘤细胞自噬作用有关。

Objective To investigate the effect of alpha fetal protein monoclonal antibody modified poly（lactic-coglycolic acid）nanoparticles carrying recombinant human decorin gene（AFPmAb-PLGA-rhDCN）on the growth and autophagy of transplanted liver tumor in mice. Methods Mouse model of transplanted liver tumor was established. AFPmAb-PLGArhDCN nanoparticles was injected to the central and the base of the tumor,using Ig G-PLGA-rhDCN nanoparticles,PLGA-empty plasmid and PBS buffer as controls. The tumors were measured for size and weighed,in which the expression of Beclin1,a protein associated with autophagy,was determined by immunohistochemical assay and Western blot. Results Compared with those in control groups, the tumor of mice treated with AFPmAb-PLGA-rhDCN nanoparticles grew slowly,of which the size and weight as well as the expression level of Beclin1 decreased significantly（each P〈0. 05）. Conclusion AFPmAb-PLGA-rhDCN nanoparticles inhibited the growth of transplanted liver tumor in mice,of which the mechanism might be associated with the inhibition of autophagic activity of tumor.