Effects of arsenic trioxide on the cellular proliferation, apoptosis and differentiation of human neuroblastoma cells

被引:33
作者
Cheung, William M. W. [1 ]
Chu, Patrick W. K. [1 ]
Kwong, Yok L. [1 ]
机构
[1] Univ Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
关键词
arsenic trioxide; retinoic acid; Trk; apoptosis; PKC;
D O I
10.1016/j.canlet.2006.02.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A human neuroblastoma cell line, IMR-32, was used as an in vitro model system to study the effects of arsenic trioxide (As2O3) on aggressive human neuroblastoma. From 0.5 mu M, As2O3 exhibited a dose-dependent inhibition of IMR-32 proliferation. At concentrations of 1.5 mu M or higher, As2O3 up-regulated caspase 3, leading to cellular apoptosis. However, neurofilament-200 kDa and tyrosine hydroxylase were not up-regulated, implying minimal neuronal differentiation. Concomitantly, TrkA was downregulated and TrkB up-regulated. Pre-treatment with the protein kinase C (PKC) inhibitor Ro-31-8220 partially blocked As2O3-mediated apoptosis, meaning that As2O3 Might Signal through PKC activation. The results suggest that As2O3 might be potentially useful in neuroblastoma. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:122 / 128
页数:7
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