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 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...
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doaj-7bb4910263014ef487f6bd144f3b69d82020-11-24T21:12:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-10-011610238232384810.3390/ijms161023823ijms161023823Shikonin 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 MedicineFeng-Ying Zhang0Yi Hu1Zhong-You Que2Ping Wang3Yun-Hui Liu4Zhen-Hua Wang5Yi-Xue Xue6Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, ChinaDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, ChinaShikonin 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).http://www.mdpi.com/1422-0067/16/10/23823shikoningliomamigrationinvasionβ-cateninphosphorylated PI3K/Akt |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Feng-Ying Zhang Yi Hu Zhong-You Que Ping Wang Yun-Hui Liu Zhen-Hua Wang Yi-Xue Xue |
spellingShingle |
Feng-Ying Zhang Yi Hu Zhong-You Que Ping Wang Yun-Hui Liu Zhen-Hua Wang Yi-Xue Xue 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 International Journal of Molecular Sciences shikonin glioma migration invasion β-catenin phosphorylated PI3K/Akt |
author_facet |
Feng-Ying Zhang Yi Hu Zhong-You Que Ping Wang Yun-Hui Liu Zhen-Hua Wang Yi-Xue Xue |
author_sort |
Feng-Ying Zhang |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-10-01 |
description |
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). |
topic |
shikonin glioma migration invasion β-catenin phosphorylated PI3K/Akt |
url |
http://www.mdpi.com/1422-0067/16/10/23823 |
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