Interferon-α Promotes the Anti-Proliferative Effect of Gefitinib (ZD1839) on Human Colon Cancer Cell Lines

Vol. 69, No. 3, 2005

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Laboratory Investigation

Interferon- Promotes the Anti-Proliferative Effect of Gefitinib (ZD1839) on Human Colon Cancer Cell Lines
Jia-Lin Yang^{a, c}, Xian-Jun Qu^d, Pamela J. Russell^a, David Goldstein^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

Address of Corresponding Author

Oncology 2005;69:224-238 (DOI: 10.1159/000088070)

Key Words

Colon cancer cell line
Gefitinib
HER1/EGFR inhibitor
Interferon-
Synergism

Abstract

Objective: Interferon- alpha (IFN alpha ) 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 IFN alpha 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 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 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. IFN alpha 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 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 HER1/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 HER1/EGFR.

Author Contacts

Dr. Jia-Lin Yang, MBBS, MEd, PhD
Oncology Research Centre
Prince of Wales Hospital, Barker Street
Randwick, Sydney, NSW 2031 (Australia)
Tel. +61 2 93822624, Fax +61 2 93822629, E-Mail j.yang@unsw.edu.au

Article Information

Received: January 20, 2005
Accepted after revision: May 4, 2005
Published online: September 1, 2005
Number of Print Pages : 15
Number of Figures : 8, Number of Tables : 3, Number of References : 56

Medline Abstract (ID 16138001)

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