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The effect of combining interferon-alpha and gefitinib in human colon cancer cell lines
1Department of Gastroenterology, Affiliated Hospital of NingXia Medical University, Yinchuan (750004), China. yanglixie@sohu.com
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.
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