Expression Of SOX2,FoxM1 In Neuroblastoma And The Regulating Effects Of PI3K/AKT Signal Pathway On Both Of Them

PART ONE:EXPRESSION OF SOX2 AND FOXM1 IN NEUROBLASTOMA AND THEIR CLINICAL SIGNIFICANCEObjective: To investigate the protein expression of SOX2?Fox M1 in neuroblastoma and to analyze their relationship with clinicopathologic feature of neuroblastoma.Methods: All of 34 NB tissue samples from Children's Hospital of Chongqing Medical University between 2011 and 2016 were enrolled,and all the samples were divided into two groups: I-II?IV-S stage and III-IV stage based on INSS.IHC was used to detect the protein expression of Fox M1 and the relationship of SOX2 and Fox M1 with clinicopathologic feature of neuroblastoma were analyzed together based on a series of literature reports about SOX2.Results: Fox M1 was detected both in nucleus and cytoplasm,sepia.The expression level of Fox M1 in I-II?IV-S stage was significantly lower than that in III-IV stage(P<0.05).The expression level of SOX2 in I-II stage neuroblastoma was significantly lower than that in III-IV stage based on literature reports.Conclusion: The expressions of SOX2 and Fox M1 in III-IV stage are significantly higher than those in I-II stage,which indicate both of them have close connection with disease progression of neuroblastoma.PART TWO:THE MECHANISMS OF PI3K/AKT SIGNALPATHWAY REGULATE SOX2,FOXM1 EXPRESSION IN NEUROBLASTOMAObjective: To investigate the mechanisms of PI3K/AKT signal pathway regulating SOX2,Fox M1 expression in neuroblastoma.Methods: Human neuroblastoma SK-N-SH cell was inoculated into 20 nude mice,and they were randomly divided into four groups after tumorigenesis: LY294002 group,the control group of LY294002(C1),IGF-1 group,and the control group of IGF-1(C2).The general condition like activity,spirit and physique of tumor-bearing nude mice were observed every two days.The tumor volume,tumor weight and the weight of tumor-bearing nude mice were measured every two days.HE was used to observed the pathological feature of tumor;western blot and IHC were used to detect the protein expression of p AKT?SOX2?Fox M1 in tumor.Results: After the intervention,the general condition of nude mice in LY294002 group was better than that in C1 group while there was no obvious difference between IGF-1 group and C2 group;the tumor volume was significantly lower in LY294002 group than that in C1 group(2223.53�266.59)cm3 vs(3239.61�519.15)cm3(P<0.05),and tumor inhibition rate was 31.4%;the tumor volume was significantly higher in IGF-1 group than that in C2 group(5619.90�1181.45)cm3 vs(4118.52� 749.29)cm3(P<0.05);the expression level of p AKT,SOX2 significantly descended in LY294002 group compared with that in C1 group(P<0.05)while the expression level of Fox M1 was similar between the two groups(P> 0.05);the expression level of p AKT,SOX2 and Fox M1 were all significantly ascended in IGF-1 groups compared with that in C2 group(P<0.05).Conclusion: PI3K/AKT signal pathway may be involved in the up-regulation of SOX2,Fox M1 and promotes the growth of neuroblastoma.