Interferon-α Promotes the Anti-Proliferative Effect of Gefitinib (ZD1839) on Human Colon Cancer Cell LinesYang J.-L.a, c · Qu X.-J.d · Russell P.J.a · Goldstein D.b
aOncology Research Centre and bDepartment of Medical Oncology, Prince of Wales Hospital, and cDepartment of Surgery and Surgical Oncological Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; dDepartment of Pharmacology, College of Pharmacy, Shandong University, Jinan, People’s Republic of China
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Objective: Interferon-α (IFNα) treatment is associated with up-regulation of epidermal growth factor receptor (HER1/EGFR) expression and marked growth inhibition of colon cancer cell lines in vitro.We aimed to determine the effect of combining IFNα and gefitinib on colon cancer cell line growth. Methods: A panel of nine colon cancer cell lines were characterised for expression of HER1/EGFR and then treated with gefitinib alone, or IFNα alone, or IFNα plus gefitinib, following a pre-treatment using vehicle or IFNα. Crystal violet staining and flow cytometry were used to assess cell proliferation and expression of HER1/EGFR. The indexes and statistical assays were used to evaluate significant differences between treatment groups against vehicle control. Results: All cell lines except SW620 were HER1/EGFR positive. IFNα treatment was associated with significant up-regulation of cell surface HER1/EGFR expression in all HER1/EGFR-positive cell lines except KM12SM. Concurrent treatment with IFNα and gefitinib, or IFNα pre-treatment followed by gefitinib, or IFNα pre-treatment followed by a combination of IFNα plus gefitinib, additively or supra-additively/synergistically enhanced the sensitivity of the seven HER1/EGFR-up-regulated cell lines. Conclusion: IFNα 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 HER1/EGFR.
© 2005 S. Karger AG, Basel
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