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2B).2B). Synergistic effects, as defined by CalcuSyn, were observed in PC3 cells treated with combinations of 1 ��mol/L vorinostat and AMG 900 (1 nmol/L and 5 nmol/L) (CI = 0.375 and CI = 0.558, respectively) (Table S1) 21,22. Figure 2 Combinations of AMG 900 with HDACIs IKK inhibitor VPA and vorinostat decrease the proliferation activity and long-term clonogenic survival of PCA cells compared to single-agent use. (A and B) Proliferation activity of PCA cells after treatment with AMG 900 and VPA ... Cell death through aurora kinase inhibition may involve aborted cytokinesis progressing to apoptosis, which may not be registered as a change in a short-term proliferation assay. Therefore, we assessed the long-term effect of combination treatment on clonogenic survival in PCA cell lines. selleck inhibitor Treatment of PCA cells with 1 nmol/L AMG 900 did not result in decreased clonogenic survival; however, combinations of low-dose AMG 900 with either VPA or vorinostat resulted in a remarkably decreased clonogenic survival compared to single-agent treatment (Fig.?(Fig.2C2C and D). Subsequent analyses performed with CalcuSyn demonstrated that administration of AMG 900 (1 nmol/L) combined with VPA (1 mmol/L and 1.5 mmol/L) resulted in a strongly synergistic decrease in survival compared to the single compounds in DU-145 and PC3 cells (0.171 cells with combinations of AMG 900 (1 nmol/L) and vorinostat RVX-208 (0.5 and 1 ��mol/L) resulted in a decrease in clonogenic survival that was synergistic or moderately synergistic in all three PCA cell lines (0.340