THE INHIBITORY EFFECT OF AN EGF RECEPTOR-SPECIFIC TYROSINE KINASE INHIBITOR ON PANCREATIC-CANCER CELL-LINES WAS MORE POTENT THAN INHIBITORYANTIBODIES AGAINST THE RECEPTORS FOR EGF AND IGF-1

Conclusion, 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 effic ient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-I-R initially decreased the cell number that later was followed by an increase in L N-36, Background/Aim. The receptors and ligands of EGF and insulin-lik e growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissu e. 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. Mate rial and 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 antibo dies and an EGFR-specific tyrosine kinase inhibitor, tyrphostin B56. R esults, MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8)M or higher concentrations a dose-response patt ern was seen. Administration of B56 to MiaPaCa-2 decreased the cell nu mber by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increa se in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and incr eased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduce d 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 st imulation 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 IG F-1 with an increased cell number, but EGF-stimulated growth was not i nfluenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppr essed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.