NDLI: Novel EGFR-TK inhibitor EKB-569 inhibits hepatocellular carcinoma cell proliferation by AKT and MAPK pathways.

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Novel EGFR-TK inhibitor EKB-569 inhibits hepatocellular carcinoma cell proliferation by AKT and MAPK pathways.

Content Provider	Europe PMC
Author	Kim, Heesue Lim, Ho Yeong
Copyright Year	2011
Abstract	Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in some cancers, but not in hepatocellular carcinoma (HCC). The aim of this study was to investigate the drug potential to overcome multi-drug resistance in HCC cells. Thirteen drug-sensitive HCC cells were assessed using the CCK-8 assay. G0-G1 arrest was measured by FACS. Western blot analysis was used to detect the key enzymes in both the Ras/Raf and PI3K pathways. When establishing the IC50 of HCC to several drugs, including EKB-569, sorafenib, erlotinib, gefitinib, pazopanib, and brivanib, SK-Hep1 cells treated with EKB-569 have shown the highest (72.8%-86.4%) G0-G1 arrest and decreased the phosphorylation of AKT and ERK at the protein level. We found that EKB-569 had higher efficacy in HCC, compared to first generation, reversible EGFR-TK inhibitors. Furthermore, the combination of sorafenib and EKB-569 showed a synergistic effect to inhibit proliferation of SNU-475, previously the most resistant cell to EGFR-TKIs. Therefore, novel EKB-569 in combination with sorafenib may be able to overcome HCC resistance to EGFR-TK inhibitors.
ISSN	10118934
Volume Number	26
PubMed Central reference number	PMC3230015
Issue Number	12
PubMed reference number	22147992
Journal	Journal of Korean Medical Science [J. Korean Med. Sci]
e-ISSN	15986357
DOI	10.3346/jkms.2011.26.12.1563
Language	English
Publisher	The Korean Academy of Medical Sciences
Publisher Date	2011-11-29
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2011 The Korean Academy of Medical Sciences.
Subject Keyword	Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors (TKIs) EKB-569 Multi-drug Resistance Hepatocellular Carcinoma (HCC) Cells
Content Type	Text
Resource Type	Article
Subject	Medicine

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