Antitumor effects of combined bortezomib and tipifarnib in head and neck squamous cell carcinoma (HNSCC) cells

5581 Background: The dysregulation of the NF-κB and Ras/PI3K/AKT pathways in HNSCC supports our hypothesis that combined treatment with the proteasome inhibitor (PI) bortezomib (B) and the farnesyl transferase inhibitor (FTI) tipifarnib (T) leads to synergistic growth inhibition of HNSCC cells. Methods: Growth inhibitory effects of single agents (B 2.5–100 nM; T 0.625–5μM), combination (B+T) (B 12.5–17.5 nM; T 0.625–5 μM) or sequential treatment (B→T after 2h or T→B) were examined in three HNSCC lines (Tu212, 686LN and Sqcc/Y1) using a sulforrhodamine B assay after 72 h of drug exposure. Combination effect in cells treated concomitantly or sequentially was assessed using the combination index (C.I.: 1.0, antagonism; ≈1.0, additivity). Apoptosis was measured by flow cytometry. Relevant protein markers were evaluated by Western blot. Cell cycle analysis after flow cytometry used FlowJo software. Statistical analysis was done using a two-sided t-test. Results: Growth inhibition by B alone is...