Zoi Vasiliki, Galani Vasiliki, Vartholomatos Evrysthenis, Zacharopoulou Natalia, Tsoumeleka Eftichia, Gkizas Georgios, Bozios Georgios, Tsekeris Pericles, Chousidis Ieremias, Leonardos Ioannis, Tzakos Andreas G, Kyritsis Athanasios P, Alexiou George A
Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece.
Department of Anatomy Histology-Embryology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Biomedicines. 2021 Oct 28;9(11):1562. doi: 10.3390/biomedicines9111562.
Curcumin, a bioactive polyphenol, is known to have anticancer properties. In this study, the effectiveness of curcumin pretreatment as a strategy for radio-sensitizing glioblastoma cell lines was explored. For this, U87 and T98 cells were treated with curcumin, exposed to 2 Gy or 4 Gy of irradiation, and the combined effect was compared to the antiproliferative effect of each agent when given individually. Cell viability and proliferation were evaluated with the trypan blue exclusion assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic effects of the combination treatment were analyzed with CompuSyn software. To examine how the co-treatment affected different phases of cell-cycle progression, a cell-cycle analysis via flow cytometry was performed. Treatment with curcumin and radiation significantly reduced cell viability in both U87 and T98 cell lines. The combination treatment arrested both cell lines at the G2/M phase to a higher extent than radiation or curcumin treatment alone. The synergistic effect of curcumin when combined with temozolomide resulted in increased tumor cell death. Our results demonstrate for the first time that low doses of curcumin and irradiation exhibit a strong synergistic anti-proliferative effect on glioblastoma cells in vitro. Therefore, this combination may represent an innovative and promising strategy for the treatment of glioblastoma, and further studies are needed to fully understand the molecular mechanism underlying this effect.
姜黄素是一种具有生物活性的多酚,已知具有抗癌特性。在本研究中,探讨了姜黄素预处理作为一种使胶质母细胞瘤细胞系对放疗敏感的策略的有效性。为此,用姜黄素处理U87和T98细胞,使其接受2 Gy或4 Gy的辐射,并将联合作用与每种药物单独使用时的抗增殖作用进行比较。用台盼蓝排斥试验和3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)试验评估细胞活力和增殖。用CompuSyn软件分析联合治疗的协同效应。为了研究联合治疗如何影响细胞周期进程的不同阶段,通过流式细胞术进行细胞周期分析。姜黄素和辐射处理均显著降低了U87和T98细胞系的细胞活力。联合治疗使两种细胞系在G2/M期的停滞程度高于单独的辐射或姜黄素治疗。姜黄素与替莫唑胺联合使用的协同效应导致肿瘤细胞死亡增加。我们的结果首次表明,低剂量的姜黄素和辐射在体外对胶质母细胞瘤细胞具有强大的协同抗增殖作用。因此,这种联合治疗可能代表了一种治疗胶质母细胞瘤的创新且有前景的策略,需要进一步研究以充分了解这种作用背后的分子机制。