Downregulation of the Notch signaling pathway inhibits hepatocellular             carcinoma cell invasion by inactivation of matrix metalloproteinase-2 and -9 and             vascular endothelial growth factor.
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.
Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, He'nan 471000, PR China.
Liang
L
Zhou
De-Sheng
DS
Wang
Qing-Jun
QJ
Li
Wei
W
Sun
Yong
Y
Zhang
Ke-Feng
KF
Dou
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D004151:Dipeptides; D005419:Flavonoids; D051880:Receptors, Notch; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053829:Amyloid Precursor Protein Secretases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one