Marinowic Daniel Rodrigo, Zanirati Gabriele Goulart, Azevedo Pamella Nunes, Zanatta Ângela, Plentz Ismael, Alcará Allan Marinho, Morrone Fernanda Bueno, Scheffel Thamiris Becker, Cappellari Angélica Regina, Roehe Paulo Michel, Muterle Varela Ana Paula, Machado Denise Cantarelli, Spillari Viola Fabiana, Da Costa Jaderson Costa
Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil.
Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
Oncol Lett. 2024 Feb 28;27(4):176. doi: 10.3892/ol.2024.14309. eCollection 2024 Apr.
Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.
胶质母细胞瘤（GBM）是成人中最常见的脑肿瘤类型之一。尽管有针对这种疾病的治疗方法，但GBM仍然是最难治疗且致死率最高的肿瘤类型之一，因此，大多数患者在确诊后两年内死亡。寨卡病毒（ZIKV）感染会抑制细胞增殖并诱导细胞凋亡，尤其是在发育中的神经元细胞中，因此有可能被视为治疗GBM的一种替代方法。在本研究中，两种GBM细胞系（U-138和U-251）分别以不同的感染复数（0.1、0.01和0.001）感染ZIKV，并分析细胞活力、迁移、黏附、凋亡诱导、白细胞介素水平以及CD14/CD73细胞表面标志物表达。本研究表明，通过MTT法和三联检测法分别测定，ZIKV感染促进了U-138细胞的细胞活力丧失并增加了细胞凋亡。通过伤口愈合试验确定，未观察到细胞迁移的变化；然而，与非肿瘤细胞（Vero细胞）相比，GBM细胞系的细胞黏附有所增加。Luminex免疫分析显示，暴露于ZIKV后，IL-4的表达水平在U-251细胞（感染复数0.001）中显著增加。在所测试的细胞系中，ZIKV感染后IFN-γ的表达水平没有显著变化。此外，与Vero细胞相比，在两种GBM细胞系中均观察到表达CD14表面标志物的细胞百分比显著增加；与未感染细胞相比，尤其在U-251细胞中观察到CD73表达显著增加。这些发现表明，ZIKV感染可能导致胶质母细胞瘤细胞的细胞活力降低、CD73表达升高、细胞黏附改善以及凋亡率升高。需要进一步研究以探索ZIKV在治疗GBM中的潜在用途。
