by NDGA mGrowth of breast cancer cells inhibited by NDGA, m F its capacity t H Lt to suppress the reactivity t t of growth factors. Neuroblastoma cells are Lapatinib particularly sensitive to IGF-I and II, peptide growth factors that stimulate mitogenesis and survive. Binding to the receptor tyrosine kinase IGF-receptor autophosphorylation of IGF-I and activation of mitogen-activated protein kinase and phosphatidylinositol-3-kinase causes signal paths. MAPK regulates mitochondrial genesis, w W During the active PI-3K target apoptotic effect act as IGF tumorigencity neuroblastoma f Rdern by stimulating the proliferation, apoptosis and inhibition of motility t stimulating T. IGFs at all stages of neuroblastoma tumors and neuroblastoma cell lines expressed and k can either act as autocrine or paracrine mitogens. IGF-I and IGF IR term neuroblastoma apoptosis by preventing the activity of t of caspase 3 t Subir. IGF also regulate Th metastatic capacity t of neuroblastoma cells by stimulating actin polymerization, Verl EXTENSIONS and mobility t Lamellipodium.
Given the effects of IGF in the tumorigenesis of neuroblastoma can medicament These interventions influenced st progression Ren IGF signaling Zibotentan disease. A highly specific inhibitor of the phosphorylation IGFIR, NVP AEW541, of the tumor, the number of rows of cells. W Although the manuscript in the present study were found NVP AEW541 showed antitumor against several neuroblastoma cell lines in vitro and in vivo. However, you should not continue AEW541 NVP clinical trials. W NDGA in several growth factor receptors can chtigen k adversely, It is effective to inhibit the growth of breast cancer and the Bek cushioning IGF activity t in IR, which was effectively blocked against neuroblastoma, and almost completed Phase I dose escalation in patients with prostate cancer, no apparent dose-limiting toxicity t of t. And NDGA is interesting to consider a compound for the treatment of neuroblastoma. In this study we analyze the effects of NDGA IGF signaling and tumorigenesis in neuroblastoma.
We used SHSY5Y, Kelly and SHEP neuroblastoma cell lines. The first two cell lines are very aggressive and express high levels of IGF IR. SHEP cells are not intrinsically tumorigenic and express few IGF IR, IGF, but hh Depends for its survival and serve as a model for the lines of the IGF-dependent-Dependent cell-dependent Neuroblastoma with low IGF-dependent IR term. S is my IGF I and serum-dependent Ngiges growth of neuroblastoma cells with NVP Ngiges AEW541 NDGA and with IGF-I dependent ABH-Dependent phosphorylation of IGF IR extracellular Re-regulated kinase and Akt in the presence of Re NDGA. We found that NDGA IGF-IR activation and subsequent Activation of the MAPK and Akt inhibits. NDGA reduced proliferation, apoptosis increased Ht and decreased motility t Ht t neuroblastoma and causes reduced tumor growth in vivo xenograft. MATERIALS AND METHODS Cell culture reagents and SH SY5Y human neuroblastoma SHEP and Kelly