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Int. J. Mol. Sci. 2015, 16(10), 23823-23848; doi:10.3390/ijms161023823

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

1
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China
2
Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China
3
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China
4
Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China
*
Author to whom correspondence should be addressed.
Academic Editor: Gopinadhan Paliyath
Received: 23 July 2015 / Revised: 20 August 2015 / Accepted: 16 September 2015 / Published: 9 October 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [19645 KB, uploaded 9 October 2015]   |  

Abstract

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). View Full-Text
Keywords: shikonin; glioma; migration; invasion; β-catenin; phosphorylated PI3K/Akt shikonin; glioma; migration; invasion; β-catenin; phosphorylated PI3K/Akt
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhang, F.-Y.; Hu, Y.; Que, Z.-Y.; Wang, P.; Liu, Y.-H.; Wang, Z.-H.; Xue, Y.-X. 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. Int. J. Mol. Sci. 2015, 16, 23823-23848.

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