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Introduction
The term cancer stem cells (CSCs) was defined as the small percentage of cells within a solid tumor capable of unregulated self-renewal, leading to continued tumor growth, as well as of the generation of partially differentiated progenitor cells (1–4). Neuroblastoma (NB) is the most common extracranial solid tumor in children and accounts for 8–10% of childhood cancers. Most children with high-risk NB have poor prognosis because of its ability to regress spontaneously, transform, or therapy-resistant relapse (5). The membrane of CSCs highly expressed ATP-binding cassette (ABC) family of membrane transport proteins and multidrug resistance protein (MDRP), which can transport drugs and toxic substances outside the cell, and are not sensitive to conventional chemotherapy drugs, which is the main cause of chemotherapy failure (6). CSCs are deemed to be the source of tumor recurrence and metastasis. Only a tumor entirely eliminated of CSCs, can be cured completely. The CSC theory provides a new perspective for cancer research, and has gradually become a hot topic and a mainstream trend (7). The isolation and purification of CSCs is the foundation for targeted cure by the combine application of small molecule drugs and chemotherapeutic drugs.
XAV939 is a kind of small molecule tankyrase (TNKS) inhibitor and synthetized using a chemical genetics approach. Huang et al (8) and Chen et al (9) have verified that XAV939 could inhibit the proliferation of colon cancer cells by blocking Wnt signaling through binding to TNKS catalytic poly-ADP-ribose polymerase (PARP) domain. Tankyrase 1 (TNKS1) is a member of the TNKS family and upregulated in a variety of cancers, including multiple myeloma, plasma cell leukemia, high-grade non-Hodgkin’s lymphomas, breast cancer, colon cancer and bladder cancer (10–16). These studies suggested that TNKS1 played a role in tumor progression. Our previous studies proved that TNKS1 was overexpressed in NB cell lines and XAV939 could induce apoptosis of NB cells partly by inhibiting Wnt/β-catenin signaling through TNKS1 (17). However, it has not been reported whether XAV939 also has effect on stemness of NB CSCs, and the involved mechanism that would contribute to targeted therapy.
In the present study, we isolated, enriched and identified NB CSCs from SH-SY5Y cells. Then we repressed TNKS1 by XAV939 treatment or RNAi method, and demonstrated the inhibition effect on the stemness and...