Integrins play a fundamental role in the migration and invasiveness of glioblastoma (GBM) cells, making them suitable targets for innovative cancer therapy. The aim of this study was to evaluate the effect of the RGD homodimeric disintegrin VLO4, isolated fromVipera lebetina obtusavenom, on the adhesion, spreading, migration, and survival of LBC3, LN18, and LN229 cell lines. This disintegrin, as a potent antagonist for α5β1 integrin, showed pro-adhesive properties for these cell lines, the highest for LN229 and the lowest for LBC3. Glioblastoma cells displayed significant differences in the spreading on the immobilized VLO4 and the natural α5β1 integrin ligand, fibronectin. Solubilized VLO4 showed different cytotoxicity and pro-apoptotic properties among tested cell lines, with the highest against LN18 and none against LN229. Moreover, VLO4 revealed an inhibitory effect on the migration of LBC3 and LN18 cell lines, in contrast to LN229 cells, which were not sensitive to this disintegrin. However, LN229 migration was impaired by VLO5, a disintegrin antagonistic to integrin α9β1, used in combination with VLO4. A possible mechanism of action of VLO4 may be related to the downregulation of α5β1 integrin subunit expression, as revealed by Western blot. VLO4 also inhibited cell proliferation and induced caspase-dependent apoptosis in LBC3 and LN18 cell lines. These results indicate that targeting α5β1 integrin by related VLO4 compounds may be useful in the development of integrin-targeted therapy for glioblastoma.
整合素在胶质母细胞瘤（GBM）细胞的迁移和侵袭过程中发挥基础性作用，使其成为创新癌症治疗的适宜靶点。本研究旨在评估从钝吻蝰蛇毒中分离的RGD同源二聚体解整合素VLO4对LBC3、LN18和LN229细胞系的黏附、铺展、迁移及存活的影响。该解整合素作为α5β1整合素的有效拮抗剂，对这些细胞系显示出促黏附特性，其中对LN229作用最强，对LBC3作用最弱。胶质母细胞瘤细胞在固定化VLO4与天然α5β1整合素配体纤连蛋白上的铺展行为存在显著差异。可溶性VLO4在不同细胞系中表现出差异化的细胞毒性和促凋亡特性：对LN18作用最强，而对LN229无显著影响。此外，VLO4对LBC3和LN18细胞系的迁移具有抑制作用，但LN229细胞对该解整合素不敏感。然而，当与拮抗整合素α9β1的解整合素VLO5联用时，LN229的迁移能力受到抑制。Western blot分析表明，VLO4可能通过下调α5β1整合素亚基表达发挥作用。VLO4还能抑制LBC3和LN18细胞系的增殖，并诱导caspase依赖性凋亡。这些结果表明，通过相关VLO4化合物靶向α5β1整合素，可能有助于开发针对胶质母细胞瘤的整合素靶向疗法。
肿瘤(癌症)患者之家