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Novel EGFR-TK Inhibitor EKB-569 Inhibits Hepatocellular Carcinoma Cell Proliferation by AKT and MAPK Pathways
Article de En | WPRIM | ID: wpr-227749
Bibliothèque responsable: WPRO
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.
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Texte intégral: 1 Indice: WPRIM Sujet Principal: Phosphorylation / Pyridines / Benzènesulfonates / Protocoles de polychimiothérapie antinéoplasique / Carcinome hépatocellulaire / Résistance aux médicaments antinéoplasiques / Mitogen-Activated Protein Kinases / Lignée cellulaire tumorale / Prolifération cellulaire / Synergie des médicaments Limites du sujet: Humans langue: En Texte intégral: Journal of Korean Medical Science Année: 2011 Type: Article
Texte intégral: 1 Indice: WPRIM Sujet Principal: Phosphorylation / Pyridines / Benzènesulfonates / Protocoles de polychimiothérapie antinéoplasique / Carcinome hépatocellulaire / Résistance aux médicaments antinéoplasiques / Mitogen-Activated Protein Kinases / Lignée cellulaire tumorale / Prolifération cellulaire / Synergie des médicaments Limites du sujet: Humans langue: En Texte intégral: Journal of Korean Medical Science Année: 2011 Type: Article