Downregulation of the Notch signaling pathway inhibits hepatocellular carcinoma cell invasion by inactivation of matrix metalloproteinase-2 and-9 and vascular endothelial growth factor

被引:68
作者
Zhou, Liang [1 ,2 ]
Wang, De-Sheng [1 ]
Li, Qing-Jun [1 ]
Sun, Wei [1 ]
Zhang, Yong [1 ]
Dou, Ke-Feng [1 ]
机构
[1] Fourth Mil Med Univ, Dept Hepatobiliary Surg, Xijing Hosp, Xian 710032, Shannxi, Peoples R China
[2] 155 Cent Hosp PLA, Dept Gen Surg, Kaifeng 471000, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Notch signaling pathway; matrix metalloproteinase; vascular endothelial growth factor; extracellular signal-regulated kinase; invasion; hepatocellular carcinoma; ACTIVATED PROTEIN-KINASE; PANCREATIC-CANCER CELLS; TUMOR-SUPPRESSOR; KAPPA-B; METASTASIS; EXPRESSION; MATRIX-METALLOPROTEINASE-9; PROLIFERATION; MIGRATION; ERK;
D O I
10.3892/or.2012.1880
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:874 / 882
页数:9
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