Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies. The main cause of death in HCC patients is tumor progression with invasion and metastasis. However, the underlying mechanisms of HCC invasion and metastasis are still not fully understood. Some studies show that the Notch signaling pathway may participate in tumor invasion and metastasis. However, the mechanisms by which the Notch signaling pathway mediates tumor cell invasion, especially in hepatocellular carcinoma, are not yet known. In the current study, we investigated the anti-invasion effect of the downregulation of the Notch signaling pathway by DAPT in HCC cells. The Notch signaling pathway inhibitor could suppress invasion of HCC cells via the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathways, resulting in the downregulation of matrix metalloproteinase-2 and -9 (MMP-2 and -9) and vascular endothelial growth factor (VEGF). These observations suggested that inhibition of the Notch signaling pathway by DAPT would be useful for devising novel preventive and therapeutic strategies targeting invasion of HCC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid Precursor Protein Secretases / antagonists & inhibitors
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Antineoplastic Agents / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Movement*
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Cell Proliferation
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Cell Survival / drug effects
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Dipeptides / pharmacology
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Down-Regulation*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Flavonoids / pharmacology
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Gene Expression / drug effects
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Hep G2 Cells / drug effects
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism*
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Neoplasm Invasiveness
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Signal Transduction / drug effects*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism*
Substances
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Antineoplastic Agents
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Dipeptides
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Flavonoids
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Receptors, Notch
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Calcium-Calmodulin-Dependent Protein Kinases
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Extracellular Signal-Regulated MAP Kinases
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Amyloid Precursor Protein Secretases
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MMP2 protein, human
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one