Downregulation of the Notch signaling pathway inhibits hepatocellular carcinoma cell invasion by inactivation of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor.
Downregulation of the Notch signaling pathway inhibits hepatocellular carcinoma cell invasion by inactivation of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor.
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DOI：
10.3892/or.2012.1880
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发表时间：
2012-09
期刊：
影响因子：
4.2
通讯作者：
Liang Zhou;De-sheng Wang;Qing-jun Li;Wei Sun;Yong Zhang;K. Dou
中科院分区：
文献类型：
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作者：
Liang Zhou;De-sheng Wang;Qing-jun Li;Wei Sun;Yong Zhang;K. Dou
肝细胞癌是最常见的恶性肿瘤之一。肝癌患者的主要死亡原因是肿瘤进展并伴有侵袭和转移。然而，肝细胞癌侵袭和转移的潜在机制仍不完全清楚。有研究表明，Notch信号通路可能参与肿瘤的侵袭和转移。然而，Notch信号通路介导肿瘤细胞侵袭的机制尚不清楚，尤其是在肝细胞癌中。在目前的研究中，我们研究了DAPT下调Notch信号通路在肝癌细胞中的抗侵袭作用。Notch信号通路抑制剂可通过细胞外信号调节激酶1和2(ERK1/2)信号通路抑制肝癌细胞的侵袭，导致基质金属蛋白酶-2和-9(MMP-2和-9)和血管内皮生长因子(VEGF)表达下调。这些观察表明，DAPT对Notch信号通路的抑制将有助于设计针对肝癌侵袭的新的预防和治疗策略。
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.