Androgen Receptor Signaling Regulates The Growth Of Neuroblastoma Cells In Vitro And In Vivo

Background:Neuroblastoma is the most common extracranial tumors in children.At present about the true etiology of neuroblastoma is unclear and some genetic susceptibility factors were found to be associated with the onset of neuroblastoma.Many studies have tried to find effective treatments for these primary malignant tumors.Although it has been illustrated that androgen receptor(AR)was expressed in neuroblastoma cells in some former reports,the biological role of androgen receptor in the development of neuroblastoma is not fully understood.Methods: 1.Western blot was used to detect the expression level of androgen receptor(AR)in neuroblastoma cell lines(SH SY5 Y,Neuro-2 a)and other cell lines,and the protein expression level after transfected si RNA AR;2.The proliferation ability was determined by MTT method to detect androgen(R1881)and androgen receptor antagonist(MDV3100 and ARN509)impacted on the neuroblastoma cell lines;3.A wound-healing assay was used to evaluate the effect of R1881 and the AR antagonists,ARN509 and MDV3100,on migration of both cell lines;4.Matrigel?-coated trans-well experiments was used to detect the impact of different treatments on cell invasion;5.3D Culture and Sphere-formation Assay and Soft agar colony forming experiment were used to detect the impact of different treatments on the sphere-forming capabilities of neuroblastoma cells;6.Animal xenograft models were evaluated the efficacy of androgen promoting neuroblastoma cells growing in vivo.Result: 1.High AR expression was detected in SH-SY5 Y and Neuro-2a cells;2.R1881 Promotes and AR Antagonists Inhibit the Cell Proliferation of Neuroblastoma invitro;3.R1881 Promotes and AR Antagonists Inhibit the Migratory Ability of Neuroblastoma Cell Lines;4.Androgen Promotes and AR Antagonists Inhibit the Invasive Ability of SH-SY5 Y Cells;5.Androgen promotes Cell Sphere Formation of Neuroblastoma Cells while antagonist of androgen receptor Inhibits Cell Sphere Formation;6.Androgen Promotes Neuroblastoma xenograft tumor growth.Conclusion: Our results suggest that AR signaling may involve in the progression of neuroblastoma as well as provide insight into a new target for the diagnosis and treatment of neuroblastoma patients.