BMS-275183–induced gene expression patterns in head and neck carcinoma

Abstract

Purpose BMS-275183 is an orally bioavailable taxane that has antitumor activity in preclinical cancer models. However, limited BMS-275183 studies have been performed in head and neck squamous cell carcinoma (HNSCC) cell lines. The purpose of this study is to identify the biological activity of BMS-275183 on HNSCC. Materials and Methods Head and neck squamous cell carcinoma cell lines, HN6, HN12, and HN30, were exposed to BMS-275183. BMS-275183–induced growth suppression, cell-cycle arrest, and apoptosis were measured. Then, expression of selected proteins that were induced by BMS-275183 was determined by Western blot analysis. Results BMS-275183 suppressed proliferation and induced G 2M arrest and apoptosis in all HNSCC cell lines tested. BMS-275183 altered the expression of cell-cycle regulators, such as cyclin A and cyclin B1. The expression of E2F and p27 was decreased and increased, respectively, in all HNSCC cell lines. Cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) were increased in HN6 and HN12 cells. epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) expression were decreased by BMS-275183 in HN6 and HN30 cell lines, whereas phosphorylated epidermal growth factor receptor (pEGFR) was decreased in only HN6 cells. Conclusions BMS-275183 induced cellular apoptosis, cell-cycle arrest, and altered gene expression in HNSCC via molecular pathways similar to other taxanes. These preclinical experiments suggest that BMS-275183 may be useful in treating HNSCC and that the aforementioned genes can potentially be used as surrogate end-point biomarkers.