Aurora A shRNA knockdown and treatment with the specific aurora A inhibitor MLN8237 similarly alter the effects of paclitaxel monotherapy as well as the combined effects of paclitaxel and pazopanib. (A) Impact of aurora A shRNA knockdown on the effects of paclitaxel alone (KTC2 cells). Inset, results of immunoblotting for aurora A compared to actin loading control in parental/(nontargeted) cells compared to three shRNA aurora A knockdown clones (sh2 to sh4). (B) Effects of aurora A shRNA knockdown on combined paclitaxel/pazopanib synergy. (C) Aurora A inhibition by MLN8237 results in synergy with paclitaxel in KTC2 ATC cells as assessed by median-effect analysis. (D) Impact of aurora A inhibition by MLN8237 (25 nM) compared to that of pazopanib (2.5 µM) on the effects of paclitaxel in KTC2 ATC cells. In (B) and (C), median-effect analysis results per Chou and Talalay (13) are shown: CI values of 1, <1, or >1 indicate additivity, synergy, or antagonism, respectively. In (A) and (D), error bars indicate 1 sample SD; +P < 0.05, *P < 0.01 relative to controls. All panels show representative results of more than three replicate assays.