Aurk inhibition blocks Myc-driven proliferation. (A) Primary Eμ-Myc lymphoma cells (having either wild-type or mutant p53) were cultured ex vivo until feeder-independent lines were established. These were treated for 24 hours with the indicated concentrations of the AKI AS703569. Effects on proliferation were assessed using an MTT assay. Shown is a representative experiment of 3 experiments performed. Bars represent the mean ± SD. (B) Proliferation of primary ex vivo cultured Eμ-Myc lymphoma cells treated for the indicated times with 25nM AS703569 (AKI). Control cells (gray bars) were left untreated for 48 hours. Bars represent the mean ± SEM percentage of cells compared with input cells set as 100% of 3 independent experiments. *Significant difference compared with control cells (P < .01). (C) Rat-1 fibroblasts were stably infected with the retroviruses expressing the indicated oncogenes and were then treated with the indicated doses of the AKI AS703569. Top panel: Immunoblot analysis of c-Myc levels. Actin was used as a loading control. Bottom panel: Percentage of Rat-1 cells in S phase assessed by PI staining for DNA content. (D) The antiproliferative effect of the AKI AS703569 in Rat-1 cells driven by the indicated oncogenes. Asynchronously growing cells were treated with AKI AS703569 at the indicated concentrations (white, black, and gray bars) for 48 hours and assessed for cell death by flow cytometric analysis of DNA content (PI). Bars represent the mean percentage of cells with a sub-G1 DNA content ± SD of 3 independent experiments. *P < .05 of Myc-infected cells compared with other cells.
