The use of anti-receptor Antique rpern, antisense nucleotides, inhibit ligand mimetic compounds, the protein LY404039 molecules IGFbinding and small. A related pair of relatively specific and potent inhibitors of IGF IR, NVP ADW742, AEW541 and NVP, inhibit the growth of a variety of tumors in vitro and in vivo, including normal fibrosarcoma and neuroblastoma normal. However, relatively few agents have been identified, the impact against IGF IR and clinical studies of NVP very specific compounds are not provided. Given the promising results against pr Clinical treatment of b Sartigen tumors IGF agents must also be characterized by many candidates, hen the chances of sustainability opportunities M, clinical efficacy and low toxicity t Erh combine t. NDGA had a long history of use was found to inhibit lipoxygenase recently tyrosine phosphorylation of IGF IR. NDGA was tested as a potential anticancer agent in several studies, where it induces apoptosis and inhibits mitogenesis.
Some of these studies have suggested that the suppression of prostaglandin synthesis can be responsible for the transmission of lipoxygenase inhibition of tumor growth. We find in this study that has the inhibition of lipoxygenase inhibitors NDGA with nonspecific no significant impact on the growth of neuroblastoma. Rather T, we suggest that the antitumor effect of NDGA in neuroblastoma mediated at BMS-790052 least in part through inhibition of IGF IR. Neuroblastoma cells are strongly dependent Ngig Ngig growth paracrine and autocrine IGF, and it is therefore logical that agents such as NVP-AEW541 and NDGA is the apprehension Higt that activation of the IGF IR tumorigenesis are prevented roblastoma new. Neuroblastoma cell lines secrete IGF II available f Kompatibilit t independently Ngig serum express ngiges growth and cell lines, high IGF IR aggressive tumorigenic. We found that NDGA at low doses of the growth of neuroblastoma release on Bl over a period of several days in vitro in two states Added ligand serum and serum free IGF and the neuroblastoma autocrine growth factor support.
NDGA prevents activation in neuroblastoma cells at the same doses that inhibit the growth in vitro 1 and 2. Mediated by IGF-I in both IR and IGF ERK The growth of tumor xenografts in neuroblastoma Nacktm Usen Kelly is also suppressed by NDGA. Zus. in animals transplanted USEFUL NDGA be characterized better prepare their effectiveness, impact on survival, and the F ability to inhibit F sequence pathways putative target sequence in vivo. In addition to neuroblastoma, NDGA inhibits in vitro and in vivo proliferation of other cancers, which are very sensitive to IGF isolation, lung cancer and breast Lich. IGFs are potent stimulators of the survival of neuro-blastoma, which leads to a strong activation of Akt, w During the suppression of caspase 3 activation. In neuroblastoma, NDGA caused inhibition of IGF-stimulated Akt activation and the entrance is. Apoptotic caspase 3 activation Ing tion and a sharp increase in sub-G0 cells Resul something Much the same