文章：

酪蛋白激酶2抑制剂CX-4945在胶质母细胞瘤体外及体内模型中诱导细胞凋亡并恢复血脑屏障稳态

Casein Kinase 2 Inhibitor, CX-4945, Induces Apoptosis and Restores Blood-Brain Barrier Homeostasis in In Vitro and In Vivo Models of Glioblastoma

原文发布日期：24 November 2024

DOI: 10.3390/cancers16233936

类型: Article

开放获取: 是

英文摘要：

Background:In oncology, casein kinase 2 (CK2), a serine/threonine kinase, has a dual action, regulating cellular processes and acting as an oncogenic promoter.Methods: This study examined the effect of CX-4945, a selective CK2 inhibitor, in a human U-87 glioblastoma (GBM) cell line, treated with CX-4945 (5, 10, and 15 μM) for 24 h. Similarly, the hCMEC/D3 cell line was used to mimic the blood–brain barrier (BBB), examining the ability of CX-4945 to restore BBB homeostasis, after stimulation with lipopolysaccharide (LPS) and then treated with CX-4945 (5, 10, and 15 μM).Results: We reported that CX-4945 reduced the proliferative activity and modulated the main pathways involved in tumor progression including apoptosis. Furthermore, in confirmation of the in vitro study, performing a xenograft model, we demonstrated that CX-4945 exerted promising antiproliferative effects, also restoring the tight junctions’ expression.Conclusions: These new insights into the molecular signaling of CK2 in GBM and BBB demonstrate that CX-4945 could be a promising approach for future GBM therapy, not only in the tumor microenvironment but also at the BBB level.

摘要翻译： 

背景：在肿瘤学中，丝氨酸/苏氨酸激酶酪蛋白激酶2（CK2）具有双重作用，既能调控细胞过程，又可作为致癌促进因子。 方法：本研究探讨了选择性CK2抑制剂CX-4945对人U-87胶质母细胞瘤（GBM）细胞系的影响，使用CX-4945（5、10和15 μM）处理24小时。同时，采用hCMEC/D3细胞系模拟血脑屏障（BBB），在脂多糖（LPS）刺激后使用CX-4945（5、10和15 μM）处理，以检测其恢复BBB稳态的能力。 结果：研究发现CX-4945能够降低增殖活性，并调控包括凋亡在内的肿瘤进展主要通路。此外，通过异种移植模型验证体外研究结果，证实CX-4945具有显著的抗增殖作用，并能恢复紧密连接蛋白的表达。 结论：这些关于CK2在GBM和BBB中分子信号传导的新发现表明，CX-4945不仅能在肿瘤微环境中发挥作用，还能在BBB水平产生效应，有望成为未来GBM治疗的一种新策略。

原文链接：

Casein Kinase 2 Inhibitor, CX-4945, Induces Apoptosis and Restores Blood-Brain Barrier Homeostasis in In Vitro and In Vivo Models of Glioblastoma