抗肿瘤药物和治疗的发展需要新的方法和分子,和天然来源的产品为抗肿瘤研究提供了有趣的替代品。在许多癌症模型中,胃足丹血蓝蛋白-多聚含铜糖蛋白已用于治疗性疫苗和抗肿瘤剂。
方法:我们通过用B16F10细胞系攻击C57BL/6小鼠,在实验动物中形成实体瘤,从而建立了黑色素瘤的鼠模型。在该黑色素瘤模型中,使用各种治疗方案评估了从海洋蜗牛Rapanathomasiana(RtH)和陆生蜗牛Helixaspersa(HaH)中分离出的血蓝蛋白的抗癌特性。流式细胞术,ELISA,扩散,和细胞毒性测定,以及组织学调查,也表演了。
结果:对肿瘤生长的有益作用,肿瘤发病率,在施用RtH或HaH后观察荷瘤C57BL/6小鼠的存活。产生高滴度的黑色素瘤特异性IgM抗体,促炎细胞因子,和肿瘤特异性CTL,高水平的肿瘤浸润的M1巨噬细胞增强了免疫反应和肿瘤抑制。
结论:RtH和HaH都表现出作为抗肿瘤治疗剂的应用和未来人类实验的有希望的性质。
The development of antitumor drugs and therapy requires new approaches and molecules, and products of natural origin provide intriguing alternatives for antitumor research. Gastropodan
hemocyanins-multimeric copper-containing glycoproteins have been used in therapeutic vaccines and antitumor agents in many cancer models.
METHODS: We established a murine model of melanoma by challenging C57BL/6 mice with a B16F10 cell line for solid tumor formation in experimental animals. The anticancer properties of
hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) were evaluated in this melanoma model using various schemes of therapy. Flow cytometry, ELISA, proliferation, and cytotoxicity assays, as well as histology investigations, were also performed.
RESULTS: Beneficial effects on tumor growth, tumor incidence, and survival of tumor-bearing C57BL/6 mice after administration of the RtH or HaH were observed. The generation of high titers of melanoma-specific IgM antibodies, pro-inflammatory cytokines, and tumor-specific CTLs, and high levels of tumor-infiltrated M1 macrophages enhanced the immune reaction and tumor suppression.
CONCLUSIONS: Both RtH and HaH exhibited promising properties for applications as antitumor therapeutic agents and future experiments with humans.