Scuteri Arianna, Nicolini Gabriella, Miloso Mariarosaria, Bossi Mario, Cavaletti Guido, Windebank Anthony J, Tredici Giovanni
Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Milano, Italy.
Anticancer Res. 2006 Mar-Apr;26(2A):1065-70.
Paclitaxel is an antineoplastic drug which acts by enhancing tubulin polymerization. The induction of peripheral neuropathy is the main dose-limiting side-effect of paclitaxel treatment. In this study, the neurotoxic effect of this drug in dorsal root ganglion (DRG) explants was analyzed by measuring the neurite length of DRG explants exposed to nerve growth factor (NGF). The neurotoxic effect of paclitaxel is dose- and time-dependent. Moreover, in DRG dissociated post-mitotic neurons, the molecular and morphological features of paclitaxel-induced cellular death were studied and the DRG neurons were observed to die by necrosis. On the contrary, the proliferating human neuroblastoma SH-SY5Y cells exposed to paclitaxel die by apoptosis, as reported for cortical neurons. The different response to the same stimulus of different neuronal populations underlines the importance of the biochemical and molecular phenotype of the neuronal population in determining cellular behavior and vulnerability to the same noxious stimulus.
紫杉醇是一种通过增强微管蛋白聚合作用来发挥功效的抗肿瘤药物。外周神经病变的诱发是紫杉醇治疗的主要剂量限制性副作用。在本研究中，通过测量暴露于神经生长因子（NGF）的背根神经节（DRG）外植体的神经突长度，分析了该药物在DRG外植体中的神经毒性作用。紫杉醇的神经毒性作用具有剂量和时间依赖性。此外，在DRG有丝分裂后解离的神经元中，研究了紫杉醇诱导的细胞死亡的分子和形态学特征，观察到DRG神经元因坏死而死亡。相反，如皮质神经元的报道一样，暴露于紫杉醇的增殖性人神经母细胞瘤SH-SY5Y细胞通过凋亡死亡。不同神经元群体对相同刺激的不同反应突显了神经元群体的生化和分子表型在决定细胞行为以及对相同有害刺激的易感性方面的重要性。
