EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells

• Published in: Cancer letters Vol. 169; no. 1; pp. 27 - 32
• Main Authors: ZHU, Xiao-Feng, LIU, Zong-Chao, XIE, Bin-Fen, LI, Zhi-Ming, FENG, Gong-Kan, DAJUN YANG, ZENG, Yi-Xin
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 10.08.2001
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Cycle - drug effects; Cell Cycle Proteins; Cell Division - drug effects; Chemotherapy; Cyclin-Dependent Kinase Inhibitor p27; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; ErbB Receptors - antagonists & inhibitors; G1 phase; G1 Phase - drug effects; Growth Inhibitors - pharmacology; Humans; MAP Kinase Signaling System - drug effects; Medical sciences; Microtubule-Associated Proteins - biosynthesis; Mitogen-Activated Protein Kinases - metabolism; Nasopharyngeal Neoplasms - enzymology; Nasopharyngeal Neoplasms - pathology; p27 protein; Pharmacology. Drug treatments; Phosphorylation - drug effects; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Quinazolines; Tumor Cells, Cultured - drug effects; Tumor Suppressor Proteins; Tyrphostins - pharmacology; Up-Regulation - drug effects; Antineoplastic agent; Human; Cell proliferation; Carcinoma; Enzyme; Transferases; Enzyme inhibitor; Nasopharynx; Malignant tumor; In vitro; Biological activity; Signal transduction; G1 Phase; Growth factor receptor; Epidermal growth factor; Cell cycle; Established cell line; ENT disease; Pharynx disease; Mechanism of action; Molecular domain; Protein-tyrosine kinase; Tumor cell
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/s0304-3835(01)00547-x

Nasopharyngeal carcinoma (NPC), which occurs with a high incidence in southern China and southeast Asia, is of epithelial origin with overexpression of EGF receptor. To study the effect of inhibition of EGFR signaling on nasopharyngeal carcinoma cell proliferation and cell cycle distribution, EGFR tyrosine kinase inhibitor AG1478 was employed to treat Nasopharyngeal Carcinoma CNE2 cells. The results showed that AG1478 inhibited proliferation of CNE2 cells. Immunoblot showed that AG1478 inhibited EGFR phosphorylation in CNE2 cells without reduced expression of EGFR protein. The activation of Akt and MAPK which are downstream molecules of EGFR signaling pathway, were also inhibited by AG1478. AG1478 induced cell cycle arrest in G1 phase, and the levels of protein p27 were significantly up-regulated. We concluded that inhibition of the EGFR signaling induced cell cycle arrest in G1 phase in CNE2 cells and p27 up-regulation was involved in this process. The EGFR kinase specific inhibitor is of potential to be developed into drugs for NPC treatment.