Ondria [38]. In our study we found that VX-680 induced the mitochondrial depolarization and finally resulted in caspase pathway activation. Phosphatidylinositol 3-kinase (PI3K)/ AKT signaling pathway plays crucial roles in cell growth, migration and invasion [24,37]. Akt is significant for regulating growth factor-stimulated cell survival response though its substrates proteins such as GSK-3, Bad and forkhead transcription factors [39]. It has been reported that high expression of Akt is relative with survival, proliferation of leukemic cells in AML and inhibition of activation of Akt can result in suppression of cell growth [40,41]. In the present study, phosphorylation of Akt-1 and GSK3b, the downstream of Akt-1, was decreased in VX-680 treated NB4-R2 cells. In addition, we also found that Akt signaling inhibitor API-2 could inhibit Akt-1 phosphorylation and induced apoptosis (data not show), indicating NB4-R2 cell apoptotic death induced by VX-680 might be due to down-regulation of Akt activation in NB4-R2 cells.Conclusions Taken together, we showed that Aurora kinase-directed small-molecule inhibitor VX-680 suppressed cell growth, and induced apoptosis in NB4-R2 cells, offering an opportunity for a novel approach targeting Aurora signaling pathway in ATRA-resistant APL treatment.Additional materialAdditional file 1: Figure S1 – VX-680 does not effectively suppress the proliferation in MCF-7 and Hela cells. MCF-7 and Hela cells were incubated with increasing doses of VX-680 (1, 2, 5 and 10 nM) for 24 hr. Cell viability was measured by MTT assay. Data summarized three independent experiments, *p < 0.05, compared to control.Abbreviations ATRA: all-trans retinoid acid; APL: acute promyelocytic leukemia; Aur: Aurora; PARP: poly ADP ribose polymerase; PML/RAR: promyelocytic leukemiaretinoid acid receptor ; AML: acute myeloid leukemia; CML: chronic myeloid leukemia; DMSO: dimethlsulfoxide; NF-B: nuclear factor-B. Acknowledgements We thank Jun-Xia Cao, Jin-E Yao, Min-Yan, Yan-Zhao, Jie-Xu, Fei-Meng Zheng and other members of Liu laboratory for their critical comments and technical support. We thank Shu-Peng Chen (Cancer Center, Sun Yat-sen University) for his technical support. We thank Dr. Ting-Xi Liu (Ruijin BMS-214662 site Hospital, Shanghai) for kindly providing NB4 and NB4-R2 cell lines. This work was supported by Chinese NSF 30873084 (to Q.L.), NSF 30670997 (to D.-R.X.), and NSF 81000217 (to Z.-J.L.). Author details State Key Laboratory of Oncology in South China, Cancer Center, Sun Yatsen University, 651 Dongfeng Road East, Guangzhou 510060, China. 2 Department of Hematology, First Affiliated Hospital, Sun Yat-sen University, 58 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27484364 Zhongshan II Road, Guangzhou 510080, China. 3Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China. 4Sun Yat-sen Institute of Hematology, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.Xu et al. Journal of Translational Medicine 2011, 9:74 http://www.translational-medicine.com/content/9/1/Page 11 ofAuthors’ contributions DRX participated in analysis and interpretation of data, and critical revision of the manuscript. SH, ZJL, JJC and ZZZ have made substantial contributions to acquisition of data. JL and DJL participated in critical analysis of results. QL participated in conception and design, analysis and interpretation of data, and critical revision of the manuscript. All authors read and approved the final manuscript. Competing interests The.