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

Nasopharyngeal carcinoma (NPC), which occurs with a high incidence in south ern China and southeast Asia, is of epithelial origin with overexpression o f EGF receptor. To study the effect of inhibition of EGFR signaling on naso pharyngeal carcinoma cell proliferation and cell cycle distribution, EGFR t yrosine kinase inhibitor AG1478 was employed to treat Nasopharyngeal Carcin oma CNE2 cells. The results showed that AG1478 inhibited proliferation of C NE2 cells. Immunoblot showed that AG1478 inhibited EGER phosphorylation in CNE2 cells without reduced expression of EGFR protein. The activation of Ak t and MAPK which are downstream molecules of EGFR signaling pathway, were a lso inhibited by AG1478. AG1478 induced cell cycle arrest in G1 phase, and the levels of protein p27 were significantly up-regulated. We concluded tha t 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 ki nase specific inhibitor is of potential to be developed into drugs for NPC treatment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.