Signaltransduksjon fra EGF-reseptor som angrepspunkt for antitumor-midlet gefitinib

Abstract

ABSTRACT

Human carcinomas frequently overexpress the EGF receptor. Preclinical studies have shown that blocking of the EGF receptor may inhibit the malignant growth in model system in vivo and in vitro. One way to inhibit the EGF receptor is to use a low-molecular weight EGF inhibitor as gefitinib (Iressa, ZD1839). In this study I have looked at the effect of gefitinib on hepatocytes and hepatoma cells (MH1C1) in rats. I have also studied using Western blotting the activation of Erk (subtype of MAP kinases), which is important for several fundamental functions in cells, including cell proliferation. While working with the Western blot, I experienced some detection problems. Bands disappeared rapidly after the detection process. In this research I have suggested hypotheses and interventions to the problem but without succeeding to find a proper answer of this matter. Other detected abnormal bands were easily corrected and described in this research. I have seen with my investigation that in the presence of gefitinib the EGF receptor-mediated activation of Erk is more sensitive in MH1C1 cells than in hepatocytes. In MH1C1 cells this total inhibition occur at 10-6 M gefitinib, with half-maximal inhibition between 10-8 M and 10-6 M. The hepatocytes is inhibited totally at the concentration 10-5 M of gefitinib and the half-maximal inhibition is between 10-7 M and 10-6 M.