NF-κB Signaling Pathway Mediated Proliferation And Invasion And Metastasis Of Neuroblastoma

A research of the NF-k B, COX-2 and MMP-9 expression and clinical significance in the neuroblastoma tissuesObjective To investigate the NF-κB(p65), COX-2 and MMP-9 expression and clinical significance of neuroblastoma tissue.Methods Immunohistochemical detection of NF-κB, COX-2 and MMP-9 expression in paraffin-embedded specimens of 80 cases of neuroblastoma tissues and 20 cases Ganglioneuroma tissue from the affiliated Hospital of Qingdao University. Analysis the relations between the age, gender, tumor size, tumor INSS stage, Shimade histological type, lymph node metastasis, invasion and the expression of NF-κB,COX-2 and MMP- 9, then, compare the association of the expression of NF-κB expression and COX-2 and MMP-9.Results Stong staining of NF-κB(p65), COX-2, MMP-9 expression was detection in neuroblastoma tissue than ganglioneuroma, the difference was statistically significant(P <0.01); the expression NF-κB(p65), COX-2, MMP-9 were associated with INSS stage cancer patients, Shimade histological type, lymph node metastasis,invasion-related, regardless of age, gender, tumor size, and the difference was statistically significant(P <0.01); Correlation analysis NF-κB(p65) expression of COX-2, MMP-9 expression, we found that NF-κB(p65), COX-2, MMP-9 protein expression was positively correlated(R = 0.626, P <0.01 AND R = 0.612, P <0.01).Conclusion 1. NF-κB(p65), COX-2, MMP-9 protein expression and tumor were higher than Ganglioneuroma in neuroblastoma tissue; 2. Blocking NF-ΚB signaling pathway can be used as a new to guidance treat and prevent the invasion and metastasis of neuroblastoma.Impact of the role and mechanism of NF-κB signaling pathway in neuroblastoma proliferation, invasion, metastasisObjective To investigate mechanism of the NF-κB signaling pathway in neuroblastoma proliferation, invasion, metastasis.Methods To detect and compare the invasion abilty of the highly metastatic neuroblastoma cells QDDQ-NM1 and low metastatic cell lines QDDQ-NM2 with transwell, CCK-8 to detection different the two cell lines proliferation, Western blort detect NF-κB(p65) and p-Ik B expression differences. With different concentrations(5,10,20,40μmol/L), NF-κB signaling pathway inhibitor PDTC pretreatment QDDQ-NM1 highly metastatic and QDDQ-NM2 low metastatic cell lines, transwell detect invasive ability to observe changes in both cell lines, Real time PCR, western blort QDDQ-NM1 QDDQ-NM2 highly metastatic and low metastatic cell lines NF-κB(p65), p-Ik Ba, COX-2, MMP-9 expression pretreated with different concentrations of PDTC differences. Select highly metastatic neuroblastoma cell line SH-SY5 Y, TNF-a pretreated different time and concentration SH-SY5 Y, improve the NF-κB signaling pathway activation level, Real time PCR and Western blort detection NF-κB(p65), p-Ik Ba, COX-2, MMP-9 gene expression, changes in transwell invasion ability to detect cell lines. THP-1 cell line induced macrophages and SH-SY5 Y cells were co-cultured to simulate in vivo tumor microenvironment, Real time PCR and Western blort detection under different processing NF-κB(p65), p-Ik Ba, COX-2,MMP-9 gene expression changes.Results The proliferation and invasion ability of neuroblastoma cells highly metastatic cell line QDDQ-NM1 higher QDDQ-NM2 than low metastatic cell lines and NF-κB(p65), p-Ik B protein expression in QDDQ-NM1 higher than QDDQ-NM2(P <0.01). Different concentrations of NF-κB inhibitor PDTC pretreatment of NF-κB signaling pathway QDDQ-NM1 highly metastatic cell lines, with the increasing concentration QDDQ-NM1 invasion of diminished capacity, protein p-IKBαgradually weakened, COX-2, MMP-9 protein expression gradually decreased(P<0.01). Different doses or time of TNF-α pretreatment QDDQ-NM1 cells, p-IKBαprotein, MMP-9, COX-2 protein in a dose and time-dependent, cell invasion ability differences among treatment groups with statistically significant(P <0.01). PMAtreated THP-1 cell line and SH-SY5 Y cells were co-cultured,co-cultured group and the control group or the treatment group compared with PDTC, MMP-9, COX-2protein expression was significantly increased(P <0.01).Conclusion 1.NF-κB signaling pathway in neuroblastoma cell lines with high metastatic invasion increased activation; 2. NF-κB nuclear transcription increase downstream gene expression of COX-2 and MMP-9, and enhance neuroblastoma proliferation, invasion and metastasis; 3. NF-κB transcription factor and COX-2 and MMP-9 can be used as treatment of neuroblastoma effective target gene for neuroblastoma treatment and provided new guidance for prognosis.