Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria.
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Mar Drugs. 2024 May 15;22(5):220. doi: 10.3390/md22050220.
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.
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 (RtH) and the terrestrial snail (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.
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.
Both RtH and HaH exhibited promising properties for applications as antitumor therapeutic agents and future experiments with humans.
抗肿瘤药物和疗法的发展需要新的方法和分子，而天然产物为抗肿瘤研究提供了有趣的选择。腹足类血蓝蛋白 - 多聚铜含糖蛋白已在许多癌症模型中用于治疗性疫苗和抗肿瘤药物。
我们通过用 B16F10 细胞系挑战 C57BL/6 小鼠来建立黑色素瘤的小鼠模型，用于实验动物中的实体瘤形成。我们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（RtH）和陆地蜗牛（HaH）中分离的血蓝蛋白的抗癌特性。还进行了流式细胞术、ELISA、增殖和细胞毒性测定以及组织学研究。
在给予 RtH 或 HaH 后，观察到对荷瘤 C57BL/6 小鼠的肿瘤生长、肿瘤发生率和生存的有益影响。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，以及高水平的肿瘤浸润 M1 巨噬细胞增强了免疫反应和肿瘤抑制。
RtH 和 HaH 均表现出作为抗肿瘤治疗剂的应用的有前途的特性，并且未来在人类中进行实验。
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