Journal
CANCER LETTERS
Volume 262, Issue 2, Pages 257-264Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2007.12.001
Keywords
HCC; cell signalling vandetanib; gefitinib; EGFR; TK inhibitors; matrix metalloproteases
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Funding
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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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.
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