EGFR and VEGFR as potential target for biological therapies in HCC cells
EGFR and VEGFR as potential target for biological therapies in HCC cells
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DOI：
10.1016/j.canlet.2007.12.001
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发表时间：
2008-04-18
期刊：
影响因子：
9.7
通讯作者：
Paradiso, Angelo
中科院分区：
文献类型：
--
作者：
Giannelli, Gianlulgi;Sgarra, Concetta;Paradiso, Angelo
肝细胞癌（HCC）是一种高度恶性、预后差的肿瘤。用于HCC治疗的EGFR和VEGFR抑制剂目前正在研究中。吉非替尼和凡德他尼抑制HCC细胞在层粘连蛋白-5和纤连蛋白上的迁移以及通过基质胶的侵袭。这两种药物在短时间内抑制p-EGFR，而它们对p-Erk 1/2和p-Akt的疗效随着时间的推移而逐渐稳定。PI 3 K/Akt和MEK/Erk 1/2抑制剂抑制迁移和侵袭以及诱导下游效应物的去磷酸化。最后，这两种抑制剂，凡德他尼和吉非替尼下调基质金属蛋白酶MMP-2和MMP-9的分泌。所有这些生物学效应似乎取决于吉非替尼和凡德他尼对p-EGFR介导的通路的阻断活性。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Hepatocellular carcinoma (HCC) is a highly malignant cancer with poor prognosis. Inhibitors of EGFR and VEGFR for HCC treatment are currently under investigation. Gefitinib and vandetanib inhibit migration of HCC cells on Laminin-5 and Fibronectin, and invasion through matrigel. Both drugs inhibit p-EGFR after short time, while their efficacy on p-Erk1/2 and p-Akt is progressive and stable over time. PI3K/Akt and MEK/Erk1/2 inhibitors, inhibit migration and invasion as well as inducing de-phosphorylation of downstream effectors. Finally, both inhibitors, vandetanib and gefitinib down-regulated the secretion of matrix metalloproteases MMP-2 and MMP-9. All these biological effects seem to depend on the activity of gefitinib and vandetanib blocking activity towards p-EGFR mediated pathways. (C) 2007 Elsevier Ireland Ltd. All rights reserved.