Dual HDAC and PI3K inhibitor CUDC-907 inhibits tumor growth and stem-like properties via suppressing PTX3 in neuroblastoma.

Abstract

Abstract Background Neuroblastoma is one of the common solid tumors in childhood and threatens the lives of children. Patients with advanced or recurrent neuroblastoma have a poor prognosis. CUDC-907, as a novel dual-target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K), has been proved to play an anti-tumor role in several tumors. However, whether CUDC-907 has anti-tumor effect in neuroblastoma is still unclear.Methods In vivo and in vitro assays were performed to investigate the anti-neuroblastoma activity of CUDC-907. PTX3 siRNA-expressing and PTX3 overexpressing plasmid were employed to define the underlying mechanisms of CUDC-907. Tumor tissues and clinical information were collected, and immunohistochemical staining was conducted to analysis the relationship between the expression of HDAC1, HDAC2, HDAC3, CD44 and prognosis of patients with neuroblastoma.Results CUDC-907 significantly inhibits proliferation, migration and promotes apoptosis of neuroblastoma cells, down-regulates the expression level of MYCN, as well as PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC-907 represses the stem-like properties of neuroblastoma cells via inhibiting PTX3, a ligand and upstream protein of cancer stem marker CD44. Immunohistochemical analysis showed that high expression of HDAC1, 2, 3 and CD44 is associated with poor prognosis of neuroblastoma patients.Conclusions These findings indicate that CUDC-907 might be developed into a possible therapeutic approach for neuroblastoma patients.