Effect of bortezomib and cetuximab in EGF-stimulated HNSCC.

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). Material s 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-diphenyltetrazoliumbromid e (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. Head and neck cancer (HNC) accounts for about 5% of all malignancies worldwide. More than 100,000 cases are diagnosed alone in Europe each year. More than 90% of the HNC are of squamous cell origin and most patients reach