Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.
Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.
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DOI：
10.3390/ijms161023823
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发表时间：
2015-10-09
影响因子：
5.6
通讯作者：
Xue YX
中科院分区：
文献类型：
--
作者：
Zhang FY;Hu Y;Que ZY;Wang P;Liu YH;Wang ZH;Xue YX
紫草素是从紫草根中提取的一种蒽醌衍生物。紫草素传统上用于治疗炎症和感染性疾病，如肝炎。紫草素还抑制各种肿瘤的增殖并诱导凋亡。然而，紫草素对胶质瘤的作用尚未完全阐明。本研究旨在探讨紫草素对人胶质母细胞瘤细胞迁移和侵袭的影响及其机制。以2.5、5和7.5 μmol/L紫草素处理U87和U251人胶质母细胞瘤细胞，采用CCK 8、划痕愈合、体外Transwell迁移和侵袭实验评价细胞活力、迁移和侵袭能力。检测基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）的表达和活性，以及磷酸化β-catenin（p-β-catenin）和磷酸化PI 3 K/Akt的表达。结果表明，紫草素能显著抑制U87和U251细胞的增殖、迁移、侵袭及MMP-2和MMP-9的表达。β-catenin在两种细胞系中的表达趋势相反。在U87细胞中明显抑制，在U251细胞中明显促进。本研究结果表明紫草素通过抑制MMP-2和MMP-9的表达和活性而抑制胶质瘤细胞的迁移和侵袭。此外，紫草素还可抑制p-PI 3 K和p-Akt的表达，从而减弱细胞的迁移和侵袭能力，并抑制MMP-2和MMP-9的表达，这种作用可被PI 3 K/Akt通路激动剂胰岛素样生长因子-1（IGF-1）逆转。
Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).