Fighting cancer from different signalling pathways: Effects of the proteasome inhibitor Bortezomib in combination with the polo-like-kinase-1-inhibitor BI2536 in SCCHN

Inhibition of the proteasome with Bortezomib as well as inhibition of Polo-like-kinase-1 (PLK-1) has been shown to be effective in many solid tumour models and also in squamous cell carcinoma of the head and neck (SCCHN) cell lines. For the first time, we systematically examined the antitumour effect of Bortezomib in combination with BI2536 in SCCHN in an in vitro study. Dose escalation studies were performed with nine SCCHN cell lines using Bortezomib and BI2536 as single agent and combination treatments. Growth-inhibitory and pro-apoptotic effects were measured quantitatively using cytohistology and Human Apoptose Array kit. The combination of Bortezomib and BI2536 showed significant anti-proliferative and apoptotic activity in all SCCHN cell lines investigated (P=0.008) compared to both the untreated control group and Bortezomib alone. A combination treatment regime consisting of the proteasome inhibitor, Bortezomib, and the inhibitor of PLK-1, BI2536, leads to an enhanced anti-proliferative and apoptotic effect in SCCHN cell lines, compared to single agent treatment with Bortezomib alone.