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Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma.
Cancer Lett. 2007 Apr 08; 248(1):32-40.CL

Abstract

Epidermal growth factor receptor (EGFR) is highly expressed in many human tumors including hepatocellular carcinoma (HCC). Therefore, inhibition of EGF receptors could be a potential target for anticancer therapy. In this study, we investigated the effects of two EGFR tyrosine kinase inhibitors, PD153035 and its analogue 4-[[3-chloro-4-fluorophenyl]amino]-6,7-dimethoxyquinazoline hydrochloride (ANAPD) on human HCC cell lines by cell proliferation assay, flow cytometry and Western blot. Our results demonstrated that both EGFR inhibitors inhibited tumor cell growth in a dose-dependent manner, but ANAPD was more potent than PD153035. These specific inhibitors not only blocked EGF-stimulated EGFR autophosphorylation but also targeted EGFR signaling including MAPK and Akt pathways. Furthermore, EGFR inhibitors induced a delay in cell cycle progression and a G(1) arrest together with a partial G(2)/M block. EGFR inhibitors also induced tumor cells to undergo apoptosis. In conclusion, this study demonstrated that both PD153035 and ANAPD inhibit tumor cell growth in HCC through inhibition of EGFR signaling pathway, and ANAPD is a more potent inhibitor than PD153035. This suggested that blockage of EGF receptors may provide an effective therapeutic approach for human HCC and ANAPD could be a potential drug candidate for the treatment of HCC.

Authors+Show Affiliations

Centre for the Study of Liver Disease, Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. ayliu@hkucc.hku.hkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16837130

Citation

Liu, Yuqing, et al. "Blockage of Epidermal Growth Factor Receptor By Quinazoline Tyrosine Kinase Inhibitors Suppresses Growth of Human Hepatocellular Carcinoma." Cancer Letters, vol. 248, no. 1, 2007, pp. 32-40.
Liu Y, Poon RT, Shao W, et al. Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. Cancer Lett. 2007;248(1):32-40.
Liu, Y., Poon, R. T., Shao, W., Sun, X., Chen, H., Kok, T. W., & Fan, S. T. (2007). Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. Cancer Letters, 248(1), 32-40.
Liu Y, et al. Blockage of Epidermal Growth Factor Receptor By Quinazoline Tyrosine Kinase Inhibitors Suppresses Growth of Human Hepatocellular Carcinoma. Cancer Lett. 2007 Apr 8;248(1):32-40. PubMed PMID: 16837130.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. AU - Liu,Yuqing, AU - Poon,Ronnie T P, AU - Shao,Weibin, AU - Sun,Xiaoli, AU - Chen,Hui, AU - Kok,Tsz Wai, AU - Fan,Sheung Tat, Y1 - 2006/07/11/ PY - 2005/11/10/received PY - 2006/05/25/revised PY - 2006/05/26/accepted PY - 2006/7/14/pubmed PY - 2007/5/5/medline PY - 2006/7/14/entrez SP - 32 EP - 40 JF - Cancer letters JO - Cancer Lett VL - 248 IS - 1 N2 - Epidermal growth factor receptor (EGFR) is highly expressed in many human tumors including hepatocellular carcinoma (HCC). Therefore, inhibition of EGF receptors could be a potential target for anticancer therapy. In this study, we investigated the effects of two EGFR tyrosine kinase inhibitors, PD153035 and its analogue 4-[[3-chloro-4-fluorophenyl]amino]-6,7-dimethoxyquinazoline hydrochloride (ANAPD) on human HCC cell lines by cell proliferation assay, flow cytometry and Western blot. Our results demonstrated that both EGFR inhibitors inhibited tumor cell growth in a dose-dependent manner, but ANAPD was more potent than PD153035. These specific inhibitors not only blocked EGF-stimulated EGFR autophosphorylation but also targeted EGFR signaling including MAPK and Akt pathways. Furthermore, EGFR inhibitors induced a delay in cell cycle progression and a G(1) arrest together with a partial G(2)/M block. EGFR inhibitors also induced tumor cells to undergo apoptosis. In conclusion, this study demonstrated that both PD153035 and ANAPD inhibit tumor cell growth in HCC through inhibition of EGFR signaling pathway, and ANAPD is a more potent inhibitor than PD153035. This suggested that blockage of EGF receptors may provide an effective therapeutic approach for human HCC and ANAPD could be a potential drug candidate for the treatment of HCC. SN - 0304-3835 UR - https://www.unboundmedicine.com/medline/citation/16837130/Blockage_of_epidermal_growth_factor_receptor_by_quinazoline_tyrosine_kinase_inhibitors_suppresses_growth_of_human_hepatocellular_carcinoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(06)00395-8 DB - PRIME DP - Unbound Medicine ER -