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-X(L), 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.
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-X(L), 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.
Authors: Nagaraj S Nagathihalli; Yugandhar Beesetty; Wooin Lee; M Kay Washington; Xi Chen; A Craig Lockhart; Nipun B Merchant Journal: Cancer Res Date: 2014-02-11 Impact factor: 12.701
Authors: Patrick J Klein; C Max Schmidt; Chad A Wiesenauer; Jennifer N Choi; Earl A Gage; Michele T Yip-Schneider; Eric A Wiebke; Yufang Wang; Charles Omer; Judith S Sebolt-Leopold Journal: Neoplasia Date: 2006-01 Impact factor: 5.715
Authors: B Nitzsche; C Gloesenkamp; M Schrader; M Ocker; R Preissner; M Lein; A Zakrzewicz; B Hoffmann; M Höpfner Journal: Br J Cancer Date: 2010-06-15 Impact factor: 7.640
Authors: Brigette B Y Ma; Vivian W Y Lui; Fan Fong Poon; S C Cesar Wong; Ka Fai To; Elaine Wong; Honglin Chen; Kwok Wai Lo; Qian Tao; Anthony T C Chan; Margaret Heung Ling Ng; Suk Hang Cheng Journal: Invest New Drugs Date: 2009-09-16 Impact factor: 3.850