Abstract:
Objective To investigate inhibitory effect of recombinant transforming growth factor α-Pseudomonas exotoxin fusion protein (TGFα-PE40;TP40) on the growth of cultured human poorly differentiated gastric carcinoma cells. Methods Expression of epidermal growth factor receptor (EGFR) in MKN-45 cells,a human poorly differentiated gastric carcinoma,was analyzed with immunohistochemistry.Inhibitory effects of TP40 on the growth of MKN-45 cells and cellular protein synthesis were analyzed with crystal violet staining and 3H-leucine incorporation.Competitive assays were performed by the over addition of EGF. Results The MKN-45 cells exhibited large amounts of brown immunoperoxidase reaction indicative of EGFR.When the concentration of TP40 was in the range of 1~100 ng/ml,TP40 inhibited the growth of MKN-45 cells and cellular protein synthesis in a dose-dependent form.Excess EGF completely blocked inhibitory effects of TP40. Conclusion The human poorly differentiated gastric carcinoma MKN-45 cells can express EGFR at high level.TP40 can significantly inhibit the growth of MKN-45 cells.The cytotoxic effects of TP40 were specifically mediated by EGFR.