Effect of bortezomib and cetuximab in EGF-stimulated HNSCC.

ABSTRACT

BACKGROUND: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, the antitumor effect of bortezomib (Velcade) in combination with cetuximab was investigated in epidermal growth factor (EGF)-stimulated head and neck squamous cell carcinoma cell lines (HNSCC). MATERIALS AND METHODS: Dose escalation studies were performed with five EGF-stimulated squamous cell carcinoma cell lines using bortezomib alone or in combination with cetuximab. Growth inhibitory and cell decline effects were measured quantitatively using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assay. RESULTS: Bortezomib alone showed no significant antiproliferative activity in any EGF-stimulated HNSCC cell line (p > 0.05), whereas the combination of bortezomib and cetuximab had highly significant antitumoral activity (p < 0.043). CONCLUSION: Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in EGF-stimulated HNSCC cell lines. A combination treatment of HNSCC with bortezomib and cetuximab may allow a therapeutical regimen to be developed that is less toxic than the conventional drugs used for these tumors.