Effects of the Polo-like-kinase-1-inhibitor BI2536 in squamous cell carcinoma cell lines of the head and neck.

Inhibition of the Polo-like-kinase-1 (PLK1) has been shown to be effective in a number of solid tumor models. In this in vitro study, we examined the antitumor effect of BI2536, a small molecule inhibitor of PLK1, in squamous cell carcinoma of the head and neck (SCCHN) cell lines. Dose escalation studies were performed with nine SCCHN cell lines using BI2536. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptosis Array Kit. BI2536 demonstrated a significant antiproliferative and apoptotic activity in all nine SCCHN cell lines investigated (p<0.009). Our results indicate that inhibition of PLK1 by BI2536 leads to an antiproliferative and apoptotic effect in SCCHN cell lines. In vivo and in the clinical setting, the application of BI2536 may support the antitumoral activity of conventional drugs that are in current use and could decrease the systemic toxicity of these drugs.

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Glucocorticoids such as dexamethasone are widely used as comedication in the treatment of head and neck cancer, e.g., to improve appetite and decrease weight loss and fatigue in patients with advanced disease or as antiallergic and antiemetic prophylaxis during anti-EGFR therapy. However, the literature suggests that dexamethasone induces resistance to antineoplastic agents in many solid tumor models in vitro and in vivo. Since this phenomenon has never been investigated in head and neck cancer, the present study was conducted to investigate the effect of dexamethasone on the antiproliferative activity of cetuximab in vitro in squamous cell carcinoma of the head and neck (SCCHN) cell lines. The antiproliferative effect of the anti-EGFR agent cetuximab alone and in combination with increasing concentrations of dexamethasone was examined in eight SCCHN cell lines at three different time-points (24, 48 and 72 h). Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Absolute tumor cell numbers were determined by cell counting in a Rosenthal chamber. Cetuximab alone inhibited the growth of all eight SCCHN cell lines significantly (p=0.008). In some cases the addition of dexamethasone reduced the antiproliferative activity of cetuximab (p