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 receptors. 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 of +38% at 10 nM EGF. Inhibition of the EGFR-associated tyrosine kinase by genistein and the tyrphostins RG-13022, RG-14620 and RG-50864 resulted in a dose-dependent growth inhibition with half maximal inhibition at 10 microM, 7 microM and 23 microM, respectively. EGF mediated growth stimulation was dose-dependently reversed by coincubation with genistein. At genistein concentrations exceeding 6 microM serum-stimulated growth of AGS cancer cells was also inhibited. We conclude that EGF is an important growth factor for AGS gastric cancer cells. Inhibition of the EGFR-associated tyrosine kinase seems to be an effective antiproliferative principle in EGFR-positive human gastric cancer cells.
Piontek
M
M
Department of Gastroenterology, University Hospital, Düsseldorf, Germany.
Hengels
K J
KJ
Porschen
R
R
Strohmeyer
G
G
D000230:Adenocarcinoma; D002396:Catechols / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000633:toxicity*; D007700:Kinetics; D009570:Nitriles / Q000633:toxicity*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D020032:Tyrphostins
D002396:Catechols; D007529:Isoflavones; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D004815:Epidermal Growth Factor; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases