Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma

We evaluated the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of neuroblastoma cells to cisplatin. Two cell lines, one derived from SH-SY5Y (SY5Y-TB8) and the other from SK-N-AS (AS-TB8), transfected with a TrkB plasmid were generated, and used to assess the effects of activation of the TrkB signal transduction path on cisplatin (Cis) induced apoptosis. BDNF treatment of each of the TrkB expressing cells blocked cisplatin-induced cell death. BDNF's ability to rescue the cells from cisplatin-induced cell death was inhibited by treatment with the Trk tyrosine kinase inhibitor, K252a, and the phosphatidylinositol 3'-kinase (PI)-3-kinase inhibitor, LY294002. This indicates that the activation of the TrkB path through PI-3-kinase is required for BDNF's survival-promoting effects. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.