title: The effect of combining interferon-alpha and gefitinib in human colon cancer cell lines.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of NingXia Medical University, Yinchuan (750004), China. yanglixie@sohu.com
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.forename: LiYa
authors.initials: L
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011799:Quinazolines; C417551:XAF1 protein, human; D066246:ErbB Receptors; D000077156:Gefitinib