Mendieta Megan, Bandegi Mehrdad, Biltekin Ezgi, Akay Yasemin M, Ozpolat Bulent, Akay Metin
Biomedical Engineering Department, University of Houston, Houston, TX 77204, USA.
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Int J Mol Sci. 2025 Jun 10;26(12):5533. doi: 10.3390/ijms26125533.
Glioblastoma Multiforme (GBM) is one of the most common brain tumors and is associated with aggressive tumor characteristics and extremely poor patient survival. The median survival time for GBM patients is around 12-15 months. Temozolomide (TMZ) is a key chemotherapeutic drug used in the treatment of GBM. However, at least 50% of GBM patients do not respond to TMZ, necessitating the identification of novel therapeutic strategies sensitizing patients to TMZ. In this study, we aimed to investigate the effects of two different tumor suppressor microRNAs (miR-329 and miR-449b) on cell proliferation and migration of GBM cells, and their potential for sensitizing GBM cells to TMZ. Our findings show that MiR-329/449b treatments suppressed spheroid formation and migration of GBM (LN229 and U87) cells. When miR treatments were combined with Temozolomide (TMZ), we also observed that they synergistically enhanced the suppressive effects of TMZ and inhibited the activity of clinically significant NF-KB and Src/FAK signaling pathways, making the combination therapy a viable option to treat GBM, with greater impact on patient survival.
多形性胶质母细胞瘤（GBM）是最常见的脑肿瘤之一，具有侵袭性肿瘤特征且患者生存率极低。GBM患者的中位生存时间约为12 - 15个月。替莫唑胺（TMZ）是治疗GBM的关键化疗药物。然而，至少50%的GBM患者对TMZ无反应，因此需要确定能使患者对TMZ敏感的新治疗策略。在本研究中，我们旨在研究两种不同的肿瘤抑制性微小RNA（miR - 329和miR - 449b）对GBM细胞增殖和迁移的影响，以及它们使GBM细胞对TMZ敏感的潜力。我们的研究结果表明，miR - 329/449b处理可抑制GBM（LN229和U87）细胞的球体形成和迁移。当miR处理与替莫唑胺（TMZ）联合使用时，我们还观察到它们协同增强了TMZ的抑制作用，并抑制了具有临床意义的NF - KB和Src/FAK信号通路的活性，使联合治疗成为治疗GBM的可行选择，对患者生存有更大影响。
