Dual targeting of EGFR and HER-2 in colon cancer cell lines.

PURPOSE: A number of studies have revealed that coexpression of EGFR and HER-2 has been found in a subset of colon cancers and may cooperatively promote tumor cell growth and survival. In the present work, two tyrosine kinase inhibitors, gefitinib and lapatinib, together with trastuzumab, raised a monoclonal antibody against HER-2 were evaluated in two colon cancer cell lines, DLD-1 and Caco-2. The aim of the study was to investigate their effect on tumor cell proliferation and apoptosis.

METHODS: Cell proliferation was assessed using the MTT assay and apoptosis was evaluated by DNA fragmentation and the Annexin V binding assay. EGFR and HER-2 protein and mRNA levels were evaluated by immunoblotting and quantitative RT-PCR, respectively.

RESULTS: Treatment of cells with each agent alone resulted in inhibition of cell proliferation after 48 h in a dose-dependent manner except for trastuzumab, which did not alter cell proliferation of DLD-1. Apoptosis increased in DLD-1 cells, after 24 h treatment with gefitinib. None of the tested agents altered apoptosis in Caco-2 cells. HER-2 and EGFR protein levels did not follow the changes of mRNA levels after treatment with the tested agents.

CONCLUSIONS: Tauhe inhibitory effect of these agents on cell proliferation and the induction of apoptosis differ for the two colon cancer cell lines under consideration. Further studies are necessary to investigate the way they exert their antitumor effect.