ANTIPROLIFERATIVE EFFECT OF TYROSINE KINASE INHIBITORS IN EPIDERMAL GROWTH FACTOR-STIMULATED GROWTH OF HUMAN GASTRIC-CANCER CELLS

AGS human gastric cancer cells were characterized to possess EGF recep tors. Scatchard analysis revealed a half saturation constant of 0.6 nM and 9000 receptors per cell. Exogenously added EGF stimulated gastric cancer cell growth in a dose-dependent manner with a maximum effect o f + 38% at 10 nM EGF. Inhibition of the EGFR-associated tyrosine kinas e by genistein and the tyrphostins RG-13022, RG-14620 and RG-50864 res ulted in a dose-dependent growth inhibition with half maximal inhibiti on at 10 mu M, 7 mu M and 23 mu M respectively. EGF mediated growth st imulation was dose-dependently reversed by coincubation with genistein . At genistein concentrations exceeding 6 mu M serum-stimulated growth of AGS cancer cells was also inhibited. We conclude that EGF is an im portant growth factor for AGS gastric cancer cells. Inhibition of the EGFR-associated tyrosine kinase seems to be an effective antiprolifera tive principle in EGFR-positive human gastric cancer cells.