In keeping with its inhibitory activity against both Aurora A and B, PHA 739358 as just one agent paid off the growth of AsPC 1 cells and increased the forming of multinucleated cells. Imatinib, as an individual representative, did not significantly influence the development of AsPC 1 cells. Nevertheless, combination treatment of PHA 739358 and imatinib induced remarkable cell death. Caspase 3/7 task assays indicated that PHA 739358 alone significantly induced apoptosis at 72 h compared to vehicle control while imatinib GW0742 didn’t. If the two drugs were combined, the induction of apoptosis further improved somewhat when compared to PHA739358 only treatment, showing that PHA739358 and imatinib act synergistically in inducing apoptosis. Moreover, combination of still another AKI, ZM447439, and imatinib also showed an important upsurge in the induction of caspase activity in comparison to either drug alone in the BxPC 3 cell line. The expression of the two anti apoptotic proteins, Bcl 2 and Bcl xL, were examined by Western blotting, to investigate the mechanism of action of the increased apoptotic effect of the combination treatment. As shown in Fig. 3C, treatment with either PHA 739358 Mitochondrion or imatinib alone did not somewhat affect the level of either protein although the combination treatment decreased the expression of Bcl 2 and Bcl xL by 73% and 68%, respectively, compared to the untreated control, showing that the improved anti apoptotic effect of the combination treatment might be an outcome of the synergistic down regulation of Bcl 2 and Bcl xL expression by both drugs. Two major effector pathways of PDGF/PDGFR signaling would be the Ras/Erk pathway and the PI3K/Akt pathway. To investigate the effect of combination treatment of imatinib and AKI on both of these pathways, we examined the phosphorylation of PI3K and Erk1/2 upon the drug treatment. As shown in Fig. 4, AsPC 1 cells treated with one agent PHA 739358 or imatinib did not somewhat influence the phosphorylation of both Erk1/2 or PI3K. But, Canagliflozin molecular weight mw combination treatment of PHA 739358 and imatinib resulted in reduced phosphorylation of PI3K however, not the ERK1/2 kinases. Similarly, mixture of ZM447439 and imatinib triggered an important loss of PI3K phosphorylation level, although not the phosphorylation of Erk kinase in the BxPC 3 cell line. These results suggest that AKIs and imatinib might act synergistically in suppressing the PI3K/Akt induced cell survival in pancreatic cancer cells. Over the past decade, more than a dozen of small molecule Aurora kinase inhibitors have now been developed and entered into medical studies.