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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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. CONCLUSION: 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.[1]


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