Abstract
Mitogen-activated protein kinases/Extracellular signal-regulated kinase (MAPK/ERK) pathway is essential for migration and invasion of malignant glioma. It is efficient to inhibit migration and invasion of glioma cells by targeting this pathway. Oleanolic acid (OA) has been well demonstrated to suppress survival, growth and angiogenesis of glioma cells. However, it is still unknown if OA affects the migration and invasion of glioma cells. We utilized U-87 MG glioma cell lines and primary glioma cells from patients to study the effect of OA on migration and invasion of glioma cells with multidisciplinary approaches. In this study, we found that OA significantly decreased the ability of glioma cells to migrate and invade. Epithelial-mesenchymal transition (EMT) of glioma cells was also suppressed by OA treatment. Furthermore, MAPK/ERK pathway was greatly inhibited in glioma cells under OA treatment. MAPK/ERK reactivation induced by a recombinant lentiviral vector, Lv-MEK, was able to rescue the inhibitory effect of OA on migration and invasion of glioma cells. Taken together, we provided evidences that OA was a MAPK/ERK pathway-targeting anti-tumor agent. Although the concentrations we used exceeded its physiological level, OA may be used to prevent migration and invasion of glioma cells by developing its derivatives with enhanced bioactivity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Cadherins / genetics
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Cadherins / metabolism
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Epithelial-Mesenchymal Transition / drug effects*
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Epithelial-Mesenchymal Transition / genetics
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression / drug effects
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Glioma / genetics
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Glioma / metabolism
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Glioma / pathology
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Humans
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Immunoblotting
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MAP Kinase Kinase 1 / genetics
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MAP Kinase Kinase 1 / metabolism
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MAP Kinase Signaling System / drug effects*
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MAP Kinase Signaling System / genetics
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Neoplasm Invasiveness
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oleanolic Acid / pharmacology*
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Tumor Cells, Cultured
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Twist-Related Protein 1 / genetics
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Twist-Related Protein 1 / metabolism
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Vimentin / genetics
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Vimentin / metabolism
Substances
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Cadherins
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Nuclear Proteins
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TWIST1 protein, human
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Twist-Related Protein 1
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Vimentin
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Oleanolic Acid
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Extracellular Signal-Regulated MAP Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
Grants and funding
This study was supported by funds from National Natural Sciences Foundation of China (No. 81001104). The website of the fund is
http://www.nsfc.gov.cn/Portal0/default152.htm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.