title: The inhibitory effect of an EGF receptor-specific tyrosine kinase inhibitor on pancreatic cancer cell lines was more potent than inhibitory antibodies against the receptors for EGF and IGF I.
abstract: CONCLUSIONS
  Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36.
  
  
  OBJECTIVE
  The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines.
  
  
  METHODS
  MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56.
  
  
  RESULTS
  MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.
authors.affiliation: Department of Surgery, University Hospital, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Kobari
authors.forename: B
authors.initials: B
authors.lastname: Kullenberg
authors.forename: A
authors.initials: A
authors.lastname: Björkman
authors.forename: S
authors.initials: S
authors.lastname: Matsuno
authors.forename: I
authors.initials: I
authors.lastname: Ihse
authors.forename: J
authors.initials: J
authors.lastname: Axelson
mesh_terms: D000906:Antibodies / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D020032:Tyrphostins; C098981:AG 556; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1