Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
Neurol Sci. 2014 Jul;35(7):1115-20. doi: 10.1007/s10072-014-1661-4. Epub 2014 Feb 11.
Despite dramatic advances in cancer therapy, the overall prognosis of glioblastoma (GBM) remains dismal. Nuclear factor kappa-B (NF-κB) has been previously demonstrated to be constitutively activated in glioblastoma, and it was suggested as a potential therapeutic target. Glycyrrhizic acid (GA) has been proved to have cytotoxic effects in many cancer cell lines. However, its role in glioblastoma has not yet been addressed. Therefore, this study aimed to investigate the effects of GA on human glioblastoma U251 cell line. The effects of GA on proliferation of U251 cells were measured by CCK-8 assay and plate colony-forming test. Cellular apoptosis was detected by Hoechst 33258 fluorescent staining and flow cytometry with annexin V-FITC/PI dual staining. The expression of nuclear p65 protein, the active subunit of NF-κB, was determined by Western blot and immunofluorescence. Our results demonstrated that the survival rate and colony formation of U251 cells significantly decreased in a time- and dose-dependent manner after GA addition, and the apoptotic ratio of GA-treated groups was significantly higher than that of control groups. Furthermore, the expression of NF-κB-p65 in the nucleus was remarkably reduced after GA treatment. In conclusion, our findings suggest that GA treatment can confer inhibitory effects on human glioblastoma U251 cell line including inhibiting proliferation and inducing apoptosis, which is possibly related to the NF-κB mediated pathway.
尽管癌症治疗取得了显著进展,但胶质母细胞瘤(GBM)的总体预后仍然不佳。核因子-κB(NF-κB)先前已被证明在胶质母细胞瘤中持续激活,并被认为是一个潜在的治疗靶点。甘草酸(GA)已被证明在许多癌细胞系中具有细胞毒性作用。然而,其在胶质母细胞瘤中的作用尚未得到解决。因此,本研究旨在探讨 GA 对人胶质母细胞瘤 U251 细胞系的影响。通过 CCK-8 测定和平板集落形成试验测量 GA 对 U251 细胞增殖的影响。通过 Hoechst 33258 荧光染色和用 Annexin V-FITC/PI 双重染色的流式细胞术检测细胞凋亡。通过 Western blot 和免疫荧光测定核 p65 蛋白(NF-κB 的活性亚单位)的表达。我们的结果表明,GA 处理后,U251 细胞的存活率和集落形成率呈时间和剂量依赖性显著降低,GA 处理组的凋亡率明显高于对照组。此外,GA 处理后核内 NF-κB-p65 的表达明显减少。总之,我们的研究结果表明,GA 处理可对人胶质母细胞瘤 U251 细胞系产生抑制作用,包括抑制增殖和诱导凋亡,这可能与 NF-κB 介导的途径有关。