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来自矛头蝮蛇毒液的 PLA-MjTX-II 对人肺癌细胞具有抗转移和抗血管生成作用。

PLA-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells.

机构信息

Institute Multidisciplinary in Health, Federal University of Bahia (UFBA), Vitória da Conquista, BA, Brazil.

Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia (UFU), Uberlândia, MG, Brazil.

出版信息

Toxicon. 2024 May 28;243:107742. doi: 10.1016/j.toxicon.2024.107742. Epub 2024 May 4.

Abstract

Phospholipases A (PLAs) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

摘要

蛇毒中的磷脂酶 A(PLAs)具有抗肿瘤和抗血管生成的特性。在这项研究中,我们评估了从 Bothrops moojeni 毒液中分离得到的 Lys49 PLA——MjTX-II 对肺癌和内皮细胞的抗转移和抗血管生成作用。通过体外和离体实验,我们证明 MjTX-II 降低了肺癌细胞(A549)的增殖,并抑制了其生长和转移的基本过程,如黏附、迁移、侵袭和肌动蛋白细胞骨架减少,而对非致瘤性肺细胞(BEAS-2B)没有明显干扰。此外,MjTX-II 引起细胞周期改变,增加活性氧的产生,调节促血管生成和抗血管生成基因的表达,并降低 HUVECs 中血管内皮生长因子(VEGF)的表达。最后,MjTX-II 抑制了主动脉环模型中的离体血管生成过程。因此,我们得出结论,MjTX-II 在体外和离体显示出抗转移和抗血管生成作用,是一种有希望作为抗肿瘤治疗药理学模型的分子。

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