Department of Oriental Medicine, Dongguk University, Kyung Ju, 780-714, Korea.
Phytother Res. 2011 Mar;25(3):429-34. doi: 10.1002/ptr.3265. Epub 2010 Aug 25.
The present study was undertaken to examine the effect of Fructus ligustri lucidi (FLL) extracts on glioma cell growth and to determine the underlying mechanism by which FLL extracts exert anticancer properties in human U87MG glioma cells. The FLL extracts resulted in cell death in a dose- and time-dependent manner. Western blot analysis showed that treatment with FLL extracts caused down-regulation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Overexpression of Akt prevented the cell death induced by the FLL extracts. The FLL extracts caused a decrease in the expression of mammalian target of rapamycin (mTOR) and the FLL extract-induced cell death was increased by the mTOR inhibitor rapamycin. The FLL extracts decreased the expression of survivin. Oral administration of FLL extracts in subcutaneous U87MG xenograft models reduced the glioma tumor volume. These findings indicate that the FLL extracts resulted in glioma cell death through regulation of the Akt/mTOR/survivin pathway in vitro and inhibited glioma tumor growth in vivo. These data suggest that the FLL extracts may serve as a potential therapeutic agent for malignant human gliomas.
本研究旨在探讨女贞子(FLL)提取物对神经胶质瘤细胞生长的影响,并确定 FLL 提取物在人 U87MG 神经胶质瘤细胞中发挥抗癌特性的潜在机制。FLL 提取物以剂量和时间依赖的方式导致细胞死亡。Western blot 分析表明,FLL 提取物处理导致磷脂酰肌醇-3 激酶(PI3K)/Akt 途径下调。Akt 的过表达可阻止 FLL 提取物诱导的细胞死亡。FLL 提取物导致雷帕霉素靶蛋白(mTOR)表达降低,mTOR 抑制剂雷帕霉素可增加 FLL 提取物诱导的细胞死亡。FLL 提取物降低了生存素的表达。FLL 提取物在皮下 U87MG 异种移植模型中的口服给药可减少神经胶质瘤肿瘤体积。这些发现表明,FLL 提取物通过调节体外 Akt/mTOR/生存素通路导致神经胶质瘤细胞死亡,并抑制体内神经胶质瘤肿瘤生长。这些数据表明,FLL 提取物可能作为恶性人类神经胶质瘤的潜在治疗剂。