Rapana thomasiana 和 Helix aspersa 的改良血青素在 B16F10 小鼠黑色素瘤模型中显示出强大的抗肿瘤活性。

IF 4.9 2区 医学 Q1 CHEMISTRY, MEDICINAL
Marine Drugs Pub Date : 2024-10-07 DOI:10.3390/md22100462
Emiliya Stoyanova, Nikolina Mihaylova, Nikola Ralchev, Silviya Bradyanova, Iliyan Manoylov, Yuliana Raynova, Krassimira Idakieva, Andrey Tchorbanov
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引用次数: 0

摘要

黑色素瘤是全球最常见的肿瘤之一,目前正在研究新的治疗方法和抗肿瘤药物。天然来源的生物大分子在抗肿瘤研究中大有可为,其中包括腹足类血蓝蛋白--在人类和小鼠癌症模型中用作抗肿瘤药物和治疗疫苗成分的高免疫原性多聚糖蛋白。我们利用在 C57BL/6 小鼠中建立的 B16F10 细胞系小鼠黑色素瘤模型来研究抗癌改性氧化血蓝蛋白(Ox-Hcs),实验动物在不同的治疗方案(100 微克/只小鼠)下服用:温和、强化和致敏。使用流式细胞术、酶联免疫吸附试验和细胞毒性试验对实体瘤生长、抗肿瘤反应、肿瘤细胞浸润和存活率进行了评估。使用 Ox-RtH 或 Ox-HaH 治疗可产生增强的特异性免疫反应(致敏组中肿瘤浸润成熟 NK 细胞(CD27+CD11b+)水平升高,强化免疫动物中巨噬细胞水平升高)和抑制肿瘤。观察到的有益效果包括延缓肿瘤的发生和生长,以及延长肿瘤动物的存活时间。在服用 Ox-Hcs 后,还观察到了高水平的黑色素瘤特异性 CTLs(可介导对肿瘤细胞的细胞毒性作用)、肿瘤浸润性 IgM 抗体(可望增强抗体依赖性细胞毒性)、M1 型巨噬细胞(可刺激 Th1 反应和细胞毒性细胞)以及促炎细胞因子。在小鼠黑色素瘤模型中,经修饰的 Hcs 在不同的给药方案中显示出强大的抗肿瘤特性,未来有望应用于人体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modified Hemocyanins from Rapana thomasiana and Helix aspersa Exhibit Strong Antitumor Activity in the B16F10 Mouse Melanoma Model.

Melanoma is one of the most common tumors worldwide, and new approaches and antitumor drugs for therapy are being investigated. Among the promising biomolecules of natural origin for antitumor research are gastropodan hemocyanins-highly immunogenic multimeric glycoproteins used as antitumor agents and components of therapeutic vaccines in human and mouse cancer models. A murine melanoma model established in C57BL/6 mice of the B16F10 cell line was used to study anticancer modified oxidized hemocyanins (Ox-Hcs) that were administered to experimental animals (100 μg/mouse) under different regimens: mild, intensive, and with sensitization. The solid tumor growth, antitumor response, cell infiltration in tumors, and survival were assessed using flow cytometry, ELISA, and cytotoxicity assays. Therapy with Ox-RtH or Ox-HaH resulted in the generation of enhanced specific immune response (increased levels of tumor-infiltrated mature NK cells (CD27+CD11b+) in sensitized groups and of macrophages in the intensively immunized animals) and tumor suppression. Beneficial effects such as delayed tumor incidence and growth as well as prolonged survival of tumor-bearing animals have been observed. High levels of melanoma-specific CTLs that mediate cytotoxic effects on tumor cells; tumor-infiltrating IgM antibodies expected to enhance antibody-dependent cellular cytotoxicity; type M1 macrophages, which stimulate the Th1 response and cytotoxic cells; and proinflammatory cytokines, were also observed after Ox-Hcs administration. The modified Hcs showed strong antitumor properties in different administration regimens in a murine model of melanoma with potential for future application in humans.

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来源期刊
Marine Drugs
Marine Drugs 医学-医药化学
CiteScore
9.60
自引率
14.80%
发文量
671
审稿时长
1 months
期刊介绍: Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.
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