Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma

Background/Aims Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors, but its effect on HCC remains unexplored. We therefore studied the antineoplastic potency of gefitinib in human HCC cells. Results Gefitinib induced a time- and dose-dependent growth inhibition of the human HCC cell lines Huh-7 and HepG2. Gefitinib-treatment induced both mitochondria-dependent and -independent apoptosis. Changes in mitochondrial membrane potential and caspase-8 activation, followed by caspase-3 activation and nuclear degradation, were detected. Moreover, gefitinib induced cell cycle arrest at the G1/S checkpoint and decreased the phosphorylation of mitogen-activated protein kinase ERK1/2. Finally, gefitinib suppressed the expression of antiapoptotic Bcl-2 and Bcl-XL, further rendering HCC cells prone to apoptosis. Conclusions Our data demonstrate that the inhibition of EGFR-TK by gefitinib induced growth inhibition, apoptosis and cell cycle arrest in human HCC cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for future treatment strategies of HCC. Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. Due to very poor 5-year-survival new therapeutic approaches are mandatory. Gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors, but its effect on HCC remains unexplored. We therefore studied the antineoplastic potency of gefitinib in human HCC cells. Gefitinib induced a time- and dose-dependent growth inhibition of the human HCC cell lines Huh-7 and HepG2. Gefitinib-treatment induced both mitochondria-dependent and -independent apoptosis. Changes in mitochondrial membrane potential and caspase-8 activation, followed by caspase-3 activation and nuclear degradation, were detected. Moreover, gefitinib induced cell cycle arrest at the G1/S checkpoint and decreased the phosphorylation of mitogen-activated protein kinase ERK1/2. Finally, gefitinib suppressed the expression of antiapoptotic Bcl-2 and Bcl-XL, further rendering HCC cells prone to apoptosis. Our data demonstrate that the inhibition of EGFR-TK by gefitinib induced growth inhibition, apoptosis and cell cycle arrest in human HCC cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for future treatment strategies of HCC.