The effect of combining interferon-alpha and gefitinib in human colon cancer cell lines

Abstract

Background and aims: Interferon-alpha (IFN-alpha) treatment is associated with up-regulation of epidermal growth factor receptor (EGFR) expression and marked growth inhibition of colon cancer cell lines. We aimed to determine the effect of combining IFN-alpha and gefitinib in the growth of human colon cancer cell lines.

Methods: Two human colon cancer cell lines SW480 and LOVO were treated with IFN-alpha alone or gefitinib alone or IFN-alpha plus gefitinib. Proliferation of colon cancer cells was measured by methyl thiazolyl tetrazolium (MTT) assay; the apoptosis rate was analysed by flow cytometry (FCM). The expression of XIAP, XAF1 mRNA was detected by RT-PCR and the expression of XlAP XAF1 protein was detected by western blotting.

Results: Methyl thiazolyl tetrazolium showed that IFN-alpha, gefitinib and IFN-alpha plus gefitinib significantly inhibited SW480 and LOVO cells in a dose-dependent manner (p < 0.05). The FCM revealed that lFN-alpha, gefitinib and IFN-alpha plus gefitinib could markedly upgrade the apoptosis rate (p < 0.05). The expression of XIAP mRNA down-regulated markedly (p < 0.05) while the expression of XAF1 mRNA up-regulated significantly (p < 0.05). The expression of XIAP protein was down-regulated markedly (p < 0.05) while the expression ofXAF1 protein was up-regulated significantly (p < 0.05).

Conclusion: IFN-alpha promotes the antiproliferaative effect of gefitinib on human colon cancer cell lines and the mechanism may be related to up-regulation expression of EGFR by IFN-alpha.