The effect of ZD1839 (Iressa™), an epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin, on apoptosis in SCC-15 cells

Abstract

The aim of this study was to determine the effect of ZD1839 on growth and apoptosis in SCC-15 (a human head and neck cancer cell line) alone, or in combination with cisplatin. High expression of the epidermal growth factor receptor has been implicated in the development of squamous cell carcinomas of head and neck. ZD1839 ('Iressa') is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways implicated in proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. Here, growth arrest was observed with 3.64 μM ZD1839. The 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) viability assay revealed a significant decrease (P < 0.001) in the percentage of surviving cells upon treatment with ZD1839 and cisplatin compared with cisplatin or ZD1839 on their own. Combined therapy of 3.64 μM ZD1839 for 24 h, prior to administration of 100 μM cisplatin, significantly (P < 0.001) and additively increased the cytotoxicity effect of cisplatin. p53-independent apoptosis was seen with cisplatin treatment, a novel finding. These data support the use of ZD1839 in anti-cancer therapy, and particularly in combination therapy. Cisplatin may induce p53-independent apoptosis. Over-expression of Bcl-2 in head and neck squamous cell carcinoma tumour cell lines is unlikely to be a general mechanism to protect these cells from apoptosis. © 2005 Blackwell Publishing Ltd.