The combination of a fluoropyrimidine with receptor tyrosine kinase inhibitors in tumor treatment has been proposed to enhance their therapeutic efficiency. The synergism of such a combination in the treatment of colorectal carcinoma is equivocal although the epidermal growth factor receptor (EGFR) is frequently overexpressed in the tumors. We used human colorectal SW 480 cells, to analyze the EGFR phosphorylation levels. We showed that incubation of cells with 5-fluorouracil (5-FU) does not influence EGFR phosphorylation of tyrosine 1173 and the overall phosphorylation after stimulation. Inhibition of EGFR phosphorylation with AG1478 reduced cell proliferation compared to 5-FU. Cells exhibited highest apoptosis rates with 5-FU. AG1479 inhibited cell proliferation more potently than 5-FU alone. Apoptosis rates after incubation with AG1478 alone and AG1478 in combination with 5-FU were significantly lower than apoptosis induction by 5-FU alone. Therefore, no synergism of both substances can be demonstrated. This experimental data argues against the combination of EGFR-inhibitors with 5-FU in a clinical setting.
Keywords: Colorectal carcinoma; EGFR phosphorylation; SW 480 cells; chemotherapy.