Erlotinib (OSI-774)-induced inhibition of transitional cell carcinoma of bladder cell line growth is enhanced by interferon-α

Abstract

OBJECTIVE: To examine whether erlotinib gives similar results to gefitinib, a small molecule epidermal growth factor receptor (HER1/EGFR) tyrosine kinase (TK) inhibitor that inhibits the growth of human bladder cancer cell lines in vitro, and given that interferon-α (IFNα) promotes an antiproliferative effect of HER1/EGFR inhibitors on colon cancer cell lines, to also determine the effects of erlotinib alone or together with INFα on bladder cancer cell lines, and whether sensitivity is influenced by HER1/EGFR mutation status. MATERIALS AND METHODS: Seven bladder cancer cell lines were characterized for HER1/EGFR expression, then treated with erlotinib alone, IFNα alone, or IFNα plus erlotinib. Cell growth inhibition was assessed by crystal-violet staining and HER1/EGFR expression by flow cytometry. Synergy was evaluated using the combination index of Chou and Talalay. DNA from these cell lines in the linear growth phase and from 14 bladder cancer tissue samples were tested for HER1/EGFRTK mutations. RESULTS: Cell-surface HER1/EGFR expression was present in all seven bladder cancer cell lines. Both erlotinib and IFNα independently were significantly antiproliferative, and combined treatment synergistically enhanced the sensitivity in six of the seven cell lines. No bladder cancer cell lines or tissues tested expressed HER1/EGFRTK mutations. CONCLUSION: Erlotinib inhibits the growth of human bladder cancer cell lines. Enhanced inhibition in the presence of IFNα is not determined by the presence of HER1/EGFRTK mutations. This study might have clinical implications for improving the treatment of bladder cancer. © 2007 The Authors.