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目的 研究噬菌体展示TM -TNF- α模拟肽的体内杀瘤效应及机制。方法 大量制备所需的噬菌体展示肽,比较不同展示肽对小鼠的肝癌细胞H2 2的体外杀瘤效应,挑取杀瘤效应最好的展示肽并选择其合适的滴度进行体内实验。小鼠接种H2 2细胞3d后,于肿瘤接种部位皮下注射噬菌体展示肽,观察肿瘤的生长情况。结果 噬菌体展示TM- TNF -α模拟肽在体内能明显抑制肿瘤的生长(P <0 .0 1)。且抑瘤率与展示肽之间呈剂量依赖关系。HE染色发现展示肽治疗组肿瘤组织中有大量淋巴细胞浸润,而sTNF- α治疗组除淋巴细胞浸润还可见中性粒细胞、浆细胞浸润。结论 直接注射噬菌体展示TM -TNF -α模拟肽可在体内有效杀瘤,其杀瘤机制可能不同于分泌型TNF -α。
Objective To study the in vivo killing effect and mechanism of phage display TM-TNF-α mimetic peptide. Methods A large number of phage displayed peptides were prepared in large quantities. The in vitro killing effect of different displayed peptides on mouse hepatoma cell line H2 2 was compared, and the best inducible peptide was selected and its suitable titer was selected for in vivo experiments. After the mice were inoculated with H2 2 cells for 3 days, the phage display peptide was injected subcutaneously into the tumor inoculation site to observe the growth of the tumor. Results Phage display TM-TNF-a mimetic peptide significantly inhibited tumor growth in vivo (P <0.01). The tumor inhibition rate showed a dose-dependent relationship with the displayed peptide. Hematoxylin-eosin staining showed that there was a large number of lymphocytic infiltration in the tumor tissue in the peptide-treated group, while neutrophil and plasma cell infiltration were seen in the sTNF-α-treated group in addition to lymphocyte infiltration. Conclusion Direct injection of phage display TM-TNF-α mimetic peptide can effectively kill tumor in vivo, and its killing mechanism may be different from secreted TNF-α.