a Department of Biochemistry and Medical Chemistry , University of Pécs , Pécs , Hungary.
Nutr Cancer. 2013;65(7):1059-66. doi: 10.1080/01635581.2013.810291. Epub 2013 Sep 13.
The goal of the present study was to compare the efficacy of treatment with irradiation (IR), temozolomide, and quercetin, alone, or in combinations, on 2 glioblastoma cell lines, DBTRG-05 and U-251. Cell viability assay, flow cytometry analysis, colony formation assay, and Western blot analysis were used to compare the effects of treatment on the 2 cell lines. The greatest reduction in cell viability and colony formation was observed when cells were treated with a combination of the agents including quercetin. The treatment of cells with the combination of IR and quercetin was equal to the efficiency of the combination of IR and temozolomide in decreasing cell viability as well as colony formation. Quercetin alone, or in combination with IR, increased the cleavage of caspase-3 and PARP-1 showing an activated apoptosis and significantly reduced the level of phospho-Akt. Moreover, these treatments increased the levels of phospho-ERK, phospho-JNK, phospho-p38, and phospho-RAF1. Our data indicate that the supplementation of standard therapy with quercetin increases efficacy of treatment of experimental glioblastoma through synergism in the induction of apoptosis via the cleavage of caspase-3 and PARP-1 and by the suppression of the actitivation of Akt pathway.
本研究的目的是比较单独或联合使用放疗（IR）、替莫唑胺和槲皮素对 2 种脑胶质瘤细胞系 DBTRG-05 和 U-251 的疗效。细胞活力测定、流式细胞术分析、集落形成测定和 Western blot 分析用于比较治疗对 2 种细胞系的影响。当用包括槲皮素在内的联合药物治疗细胞时，观察到细胞活力和集落形成的最大减少。用 IR 和槲皮素联合治疗细胞与 IR 和替莫唑胺联合治疗在降低细胞活力和集落形成方面同样有效。槲皮素单独或与 IR 联合使用可增加 caspase-3 和 PARP-1 的裂解，表现出激活的细胞凋亡，并显著降低磷酸化 Akt 的水平。此外，这些处理还增加了磷酸化 ERK、磷酸化 JNK、磷酸化 p38 和磷酸化 RAF1 的水平。我们的数据表明，用槲皮素补充标准治疗通过协同作用增加了实验性脑胶质瘤治疗的疗效，通过 caspase-3 和 PARP-1 的裂解诱导细胞凋亡，并抑制 Akt 通路的激活。
