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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 polylactic-co-glycolic acid (PLGA) -targeted nanoparticles loaded with the decorin (DCN) gene modified with alpha-fetoprotein (AFP) Effect of Mice on the Growth of Hepatocellular Carcinoma and Its Relationship with Autophagy. Methods A murine model of hepatocellular carcinoma xenografts was established. The AFP mAb-modified nanoparticles AFPmAb-PLGA-rhDCN were injected into the central and basal part of the tumor. The non-specific Ig G-PLGA rhDCN nanoparticles, PLGA-empty plasmid and PBS buffer were used as control group. The tumor volume and tumor weight were measured. The changes of autophagy-related gene Beclin1 protein in tumor tissues were detected by immunohistochemistry and Western blot. Results Compared with the three control groups, AFPmAb-PLGA-rhDCN nanoparticles showed slow tumor growth, tumor volume and tumor weight were significantly reduced (P <0.05), Beclin1 protein expression was significantly decreased (P <0.05). Conclusion AFP monoclonal antibody modified DCN nanoparticles can inhibit the growth of transplanted hepatocellular carcinoma in mice. The mechanism may be related to the inhibition of tumor cell autophagy.