Gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, up-regulates p27^KIP1 and induces G1 arrest in oral squamous cell carcinoma cell lines

Abstract 

High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). Recently, the results of preclinical studies and early clinical trials targeting the EGFR have shown evidence of the activity. In this study, gefitinib (‘Iressa’, ZD1839), an EGFR-tyrosine kinase inhibitor, inhibited cell proliferation and upregulated p27^KIP1 in OSCC cells. Growth inhibition was observed in OSCC xenografts when mice were treated with gefitinib in vivo. A flow cytometric analysis demonstrated that treatment with gefitinib induced accumulation in G1 phase, accompanied by a decrease in the percentage of cells in S phase. Apoptosis was not seen in this study. Cell growth was inhibited by an increase of the cell cycle inhibitor p27^KIP1 and a decrease of its ubiquitin ligase subunit Skp2.

Keywords:  Epidermal growth factor receptor, Tyrosine kinase inhibitor, Cell proliferation, Lymph node metastasis, Oral squamous-cell carcinoma