Erlotinib (OSI-774)-induced inhibition of transitional cell carcinoma of bladder cell line growth is enhanced by interferon-alpha.
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-alpha (IFNalpha) promotes an antiproliferative effect of HER1/EGFR inhibitors on colon cancer cell lines, to also determine the effects of erlotinib alone or together with INFalpha on bladder cancer cell lines, and whether sensitivity is influenced by HER1/EGFR mutation status.


METHODS
Seven bladder cancer cell lines were characterized for HER1/EGFR expression, then treated with erlotinib alone, IFNalpha alone, or IFNalpha 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 IFNalpha 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.


CONCLUSIONS
Erlotinib inhibits the growth of human bladder cancer cell lines. Enhanced inhibition in the presence of IFNalpha is not determined by the presence of HER1/EGFRTK mutations. This study might have clinical implications for improving the treatment of bladder cancer.
Yang
Jia-Lin
JL
Oncology Research Centre, Prince of Wales Hospital, Department of Clinical Medicine, University of New South Wales, Sydney, Australia. j.yang@unsw.edu.au
Qu
Xian-Jun
XJ
Hayes
Vanessa M
VM
Brenner
Phillip C
PC
Russell
Pamela J
PJ
Goldstein
David
D
D000704:Analysis of Variance; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors