performed nude mouse experiment. manifestation of epithelial-mesenchymal transition (EMT) markers. ICG-001 also inhibited C666-1 tumor sphere formation, accompanied with reduced SOX2hi/CD44hi CSC-like populace. ICG-001 was also found to restore the manifestation of a tumor suppressive microRNA-145 (miR-145). Ectopic manifestation of miR-145 efficiently repressed SOX2 protein manifestation and inhibited tumor sphere formation. Combination of ICG-001 with cisplatin synergistically suppressed growth of C666-1 cells and significantly suppressed growth of NPC xenografts. These results suggested that therapeutically focusing on of the CBP/-catenin signaling pathway with ICG-001 can efficiently reduce the CSC-like populace and combination with cisplatin can efficiently suppress the growth of NPC. Nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharynx. It has a relatively high prevalence in southern China with an annual incidence of >20 per 100,0001. NPC is definitely consistently associated with Epstein-Barr computer virus (EBV) latent illness. The EBV-encoded genes and cellular microRNAs (miRNAs) are believed to be involved in the pathogenesis of NPC2. C666-1 is the only EBV-positive NPC cell collection carrying native EBV genome and is preferred as a suitable model for translational study of EBV-associated NPC3. Currently, the standard treatment for NPC is definitely radiotherapy or combined chemo-radiotherapy with cisplatin-based regimens4. Although main NPC can be successfully treated with radiotherapy and chemo-radiotherapy, the treatment results for locally advanced and metastatic NPC remains unsatisfactory. High rates of local relapse and distant metastasis are the Olesoxime major concern for treatment failure5. Accumulating evidence suggested that a subpopulation of malignancy cells with self-renewal and stem-like cell properties, namely malignancy stem cells (CSCs), play an important part in tumor initiation and resistance to radio- and chemotherapy6,7. The living of CSCs may explain the high rate of tumor relapse after standard therapies8. Therapeutic targeting of the CSC populace is definitely a novel strategy to overcome restorative resistance and tumor relapse after malignancy treatment9,10. Wnt signaling is one of the important CSC self-renewal signaling pathways11. Multiple stem cell-related genes such as CD44, survivin, and c-myc are Wnt-regulated genes. Early studies within the gene manifestation profile of NPC showed that the manifestation of a number of Wnt signaling parts, including wingless-type MMTV integration site family, member 5A (Wnt5A), Frizzled homolog 7 (FZD7), -catenin, and CREB-binding protein (CBP) are frequently triggered, and the aberrant improved manifestation of -catenin is definitely associated with poor prognosis in NPC12,13,14. In addition to the overexpression of the Wnt parts, epigenetic inactivation of tumor suppressor Wnt inhibitory element-1 (WIF-1) was also found to be involved in the activation of the Wnt pathway and the metastasis of NPC15,16. In NPC, the Wnt signaling pathway was aberrantly triggered and the manifestation of the Wnt-regulated stem cell connected genes was also found to be up-regulated17. To accomplish a better translational outcome, restorative focusing on of the Wnt signaling TRK in NPC may reduce the CSC populace and, consequently, sensitize the cells to standard treatment. Small molecules focusing on the Wnt signaling pathway have recently been launched to pre-clinical and medical studies18,19. Kahn and co-workers have previously found that ICG-001, a small molecule Wnt modulator, can securely eradicate the drug-resistant CSC-like populace and initiate cell differentiation in leukemia and solid Olesoxime malignancy models20,21,22. In the canonical Wnt pathway, nuclear -catenin binds to the coactivator CBP to Olesoxime mediate transcription of genes associated with stem cell proliferation and cell pluripotency. ICG-001 binds specifically to CBP and functions as a CBP/-catenin antagonist, which blocks transcription of genes associated with stem cell proliferation and self-renewal, therefore reducing the stem cell populace. This also facilitates the connection of -catenin with the highly homologous coactivator p300 to initiate transcription of genes associated with cell differentiation23,24. As Wnt signaling is definitely deregulated in NPC, we hypothesized that pharmacological treatment of Wnt signaling with the CBP/-catenin antagonist ICG-001 could be used to reduce the CSC-like populace. Here, we analyzed the effect of ICG-001 on growth of the EBV-positive C666-1 CSC-like populace through 3-D tumor sphere formation assay. We also found that the growth inhibitory effect of ICG-001.