Interferon-alpha promotes the anti-proliferative effect of gefitinib (ZD 1839) on human colon cancer cell lines.
OBJECTIVE
Interferon-alpha (IFN alpha) treatment is associated with up-regulation of epidermal growth factor receptor (HER 1/EGFR) expression and marked growth inhibition of colon cancer cell lines in vitro. We aimed to determine the effect of combining IFN alpha and gefitinib on colon cancer cell line growth.


METHODS
A panel of nine colon cancer cell lines were characterised for expression of HER 1/EGFR and then treated with gefitinib alone, or IFN alpha alone, or IFN alpha plus gefitinib, following a pre-treatment using vehicle or IFN alpha. Crystal violet staining and flow cytometry were used to assess cell proliferation and expression of HER 1/EGFR. The indexes and statistical assays were used to evaluate significant differences between treatment groups against vehicle control.


RESULTS
All cell lines except SW 620 were HER 1/EGFR positive. IFN alpha treatment was associated with significant up-regulation of cell surface HER 1/EGFR expression in all HER 1/EGFR-positive cell lines except KM 12 SM. Concurrent treatment with IFN alpha and gefitinib, or IFN alpha pre-treatment followed by gefitinib, or IFN alpha pre-treatment followed by a combination of IFN alpha plus gefitinib, additively or supra-additively/synergistically enhanced the sensitivity of the seven HER 1/EGFR-up-regulated cell lines.


CONCLUSIONS
IFN alpha improves the anti-proliferative effect of EGFR inhibition in colorectal cancer cell lines. This approach may have clinical implications for improving treatment based on targeting of HER 1/EGFR.
Yang
Jia-Lin
JL
Oncology Research Centre, Prince of Wales Hospital, Sydney, Australia. j.yang@unsw.edu.au
Qu
Xian-Jun
XJ
Russell
Pamela J
PJ
Goldstein
David
D
D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D007155:Immunologic Factors; D016898:Interferon-alpha; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib