Characterization of neurotoxicity induced by anticancer agents
01 / 2006 - onbekend
The aim of this study is to characterize the extend of drug induced neurotoxicity. Many antineoplastic drugs show neurotoxicity and this side effect might be dose-limiting or leading to the cessation of the treatment. Two different model systems (rat pheochromocytoma cell line PC12 and human neuroblastoma cell line SH-SY5Y) are used to determine wether different antineoplastic compounds (Oxaliplatin, EpothiloneB and Bortezomib) act differently or similarly in these model systems compared to tumor cells (U-87 Glioma cell line). PC12 cells were induced to neuronal differentiation using Nerve Growth Factor (NGF) while SH-SY5Y differentiate towards a mature neuronal phenotype with neurite elongation following the treatment with Retinoic Acid (RA). After treatment neuronal differentiation was evaluated using a morphological method requiring tracking and measuring of neurites. Differentiated cells were treated with IC50 drugs concentration showing a statistically significant decrease of neurite lenght with respect to control cells. Since quantification of neurite outgrowth is impractical on a large scale decreases in Cyclin B2 and BIRC5 can be used as model marker. The expression of these two genes is being evaluated with TaqMan RT-PCR.