Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line

Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line
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DOI:
10.1007/s10072-014-1661-4
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发表时间:
2014-07-01
影响因子:
3.3
通讯作者:
Hang, Chun-Hua
Hang, Chun-Hua
中科院分区:
医学4区
文献类型:
--
作者:
Li, Song;Zhu, Jian-Hong;Hang, Chun-Hua

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尽管癌症治疗取得了巨大进展,但胶质母细胞瘤(GBM)的总体预后仍然令人沮丧。核因子-κ B(NF-κ B)在胶质母细胞瘤中被激活,并被认为是一个潜在的治疗靶点。甘草酸(GA)已被证明对多种肿瘤细胞系具有细胞毒作用。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细胞株的作用。采用CCK-8法和平板集落形成实验检测GA对U251细胞增殖的影响。Hoechst 33258荧光染色和Annexin V-FITC/PI双染流式细胞术检测细胞凋亡。Western blot和免疫荧光法检测NF-κ B B活性亚基p65蛋白的表达。结果表明,GA处理组U251细胞存活率和集落形成率均显著低于对照组,且呈时间和剂量依赖性; GA处理组U251细胞凋亡率显著高于对照组。GA处理后,核内NF-κ B-p65的表达明显减少。结论:GA对人胶质母细胞瘤U251细胞具有抑制增殖和诱导凋亡的作用,其机制可能与NF-κ B B介导的信号通路有关。
Despite dramatic advances in cancer therapy, the overall prognosis of glioblastoma (GBM) remains dismal. Nuclear factor kappa-B (NF-kappa B) 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-kappa B, 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-kappa B-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-kappa B mediated pathway.