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维甲酸分化的SH-SY5Y人神经母细胞瘤细胞:一种评估药物神经毒性的体外模型。

Retinoic acid differentiated SH-SY5Y human neuroblastoma cells: an in vitro model to assess drug neurotoxicity.

作者信息

Nicolini G, Miloso M, Zoia C, Di Silvestro A, Cavaletti G, Tredici G

机构信息

Istituto di Anatomia Umana, Sezione di Neuroanatomia, Milano, Italy.

出版信息

Anticancer Res. 1998 Jul-Aug;18(4A):2477-81.

PMID:9703895
Abstract

PURPOSE

To evaluate whether retinoic acid (RA) differentiated human neuroblastoma (HN) SH-SY5Y cells are a suitable and reliable model to test the neurotoxicity of chemotherapic drugs without the confusing effects of the neurotrophic factors commonly used to induce neuronal differentiation.

METHODS

Cultures of the SH-SY5Y cell line were exposed to RA to induce neuronal differentiation which was assessed by measuring the neurite length. The effect of increasing concentrations of cisplatin (CDDP) on neurite outgrowth was determined. Cyclophosphamide (CTX) was used as negative control.

RESULTS

CDDP induced a significant reduction in the mean neurite length in a dose dependent manner. The neurotoxic effect of CDDP was reversible. Cyclophosphamide did not induce changes in RA differentiated HN cells.

CONCLUSIONS

RA differentiated HN cells are sensitive to the neurotoxic effect of CDDP and the course of the changes is similar to that observed in clinical practice and in in vivo experimental models. Therefore, this model is proposed as a screening method to test the neurotoxicity of chemotherapy drugs and the possible effect of neuroprotectant molecules and drugs.

摘要

目的

评估视黄酸(RA)分化的人神经母细胞瘤(HN)SH-SY5Y细胞是否是一种合适且可靠的模型,用于测试化疗药物的神经毒性,而不存在通常用于诱导神经元分化的神经营养因子的干扰作用。

方法

将SH-SY5Y细胞系培养物暴露于RA以诱导神经元分化,通过测量神经突长度进行评估。测定顺铂(CDDP)浓度增加对神经突生长的影响。环磷酰胺(CTX)用作阴性对照。

结果

CDDP以剂量依赖性方式导致平均神经突长度显著减少。CDDP的神经毒性作用是可逆的。环磷酰胺未诱导RA分化的HN细胞发生变化。

结论

RA分化的HN细胞对CDDP的神经毒性作用敏感,变化过程与临床实践和体内实验模型中观察到的相似。因此,该模型被提议作为一种筛选方法,用于测试化疗药物的神经毒性以及神经保护分子和药物的可能作用。

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