Study On The Mechanism Of Oridonin’s Antitumor Effects On Neuroblastoma

Objective:Neuroblastoma originates from the sympathetic nervous system.And it is the most common tumor in infants,the most common extracranial tumor in childhood.The treatment is mainly based on surgery,supplemented by radiotherapy and chemotherapy.It has been reported that Chinese medicine combined with chemotherapy can improve the efficacy of neuroblastoma in children.Oridonin is a diterpene with anti-microbial,anti-inflammatory and anti-tumor effects.The aim of this study is to investigate whether oridonin has an anti-tumor effect on neuroblastoma and further elucidate its specific molecular mechanism.Methods:1.CCK-8 cell proliferation assay,Annexin-V and PI staining,PI staining,TUNEL method,nude mice xenograft model and nude mice metastasis model were used to explore the anti-tumor effect of oridonin on neuroblastoma.2.Western blot,immunoprecipitation,immunohistochemistry,HE staining,real-time RT PCR,protein knockdown technology,protein overexpression technology were used to further explore the specific molecular mechanism of oridonin’s anti-neuroblastoma effects.Results:1.Oridonin inhibits the proliferation of neuroblastoma in vitro and in vivo by inducing apoptosis and cell cycle arrest.2.Oridonin causes apoptosis and cell cycle arrest by the reactivation of P53.3.Oridonin-induced MDM2 P60 maintains the continuous activation of P53 by the deubiquitination on P53.4.Oridonin up-regulates USP2 a at the post-transcriptional level by ROS,it regulates P53 through MDM2 P60 and is closely related with apoptosis.Conclusion:Oridonin exerts its anti-neuroblastoma effect by inducing apoptosis and cell cycle arrest.The re-activated P53,MDM2 P60 and USP2 a play critical roles in the whole process.