and earlier studies on TNKS1 function during mitosis. Huang et al. found that small molecule drug XAV939 didn’t cause mitotic arrest in DLD-1 colon cancer cells, neither RNAi-TNKS1 do. The results were in sharp contrast with other studies [28,

29, 31]. In the present study we also found that the three NB cell lines, when treated with XAV939, have a prolonged S phase followed by a G2/M cell cycle arrest compared to untreated cells. This discrepancy may be related to different types of Eltanexor supplier cancer and need to be further investigated. Recently it has been shown that XAV939 inhibits DLD-1 Bafilomycin A1 mouse colony formation in an axin-dependent manner [14]. Axin is a concentration-limiting factor in the β-catenin degradation complex and may function more generally as a signal ‘integrator’ in modulating Wnt pathway activity. In our studies, XAV939 as well as shRNA for TNKS1 inhibited SH-SY5Y colony formation in vitro (Figure 2). In conclusion, the present data and previous studies indicate that small molecule inhibitors XAV939 could inhibit the proliferation and colony formation of SH-SY5Y cells by inhibiting TNKS1 might in part through Wnt/β-catenin signaling. But the results are required to be validated in vivo to get a better understanding of the mechanisms involved and the potential CDK activation role of XAV939 in NB treatment. Moreover, TNKS1 is a protein that participates in both telomere regulation and Wnt/β-catenin signaling, which are essential factors

for tumor remedy and recurrence. However, the relationship between the telomere regulation and Wnt/β-catenin signaling need to be further explored. The research will pave the way for NB treatment used by TNKS1 inhibitors. Conclusions In sum, we have shown that inhibition of TNKS1 by XAV939 or RNAi method inhibits the proliferation and induces apoptosis of NB cell lines. One of the related mechanisms may be the inhibiting of Wnt/β-catenin signaling. But more experiments should be carried out to clarify the exact mechanisms. This effect would be expected to promote small Axenfeld syndrome molecule targeted therapy in patients with malignant

NB. Acknowledgments The study was supported by National Natural Science Foundation of China (30772215). The authors would like to thank Professor Yuhua Chen and Xining Pang of Departnzent of Developmental Biology in China Medical University, and people who help us. References 1. Maris JM, Matthay KK: Molecular biology of neuroblastoma. J Clin Oncol 1999, 17:2264–2279.PubMed 2. Maris JM, Hogarty MD, Bagatell R, Cohn SL: Neuroblastoma. Lancet 2007, 369:2106–2120.PubMedCrossRef 3. Sharp SE, Gelfand MJ, Shulkin BL: Pediatrics: diagnosis of neuroblastoma. Semin Nucl Med 2011, 41:345–353.PubMedCrossRef 4. Bilir A, Erguven M, Yazihan N, Aktas E, Oktem G, Sabanci A: Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in human neuroblastoma cancer cell line SH-SY5Y. J Neurooncol 2010, 100:385–395.PubMedCrossRef 5.