Effects of arsenic trioxide on the cellular proliferation, apoptosis and differentiation of human neuroblastoma cells
Effects of arsenic trioxide on the cellular proliferation, apoptosis and differentiation of human neuroblastoma cells
复制标题
DOI：
10.1016/j.canlet.2006.02.009
复制
发表时间：
2007-02-08
期刊：
影响因子：
9.7
通讯作者：
Kwong, Yok L.
中科院分区：
文献类型：
--
作者：
Cheung, William M. W.;Chu, Patrick W. K.;Kwong, Yok L.
以人神经母细胞瘤细胞系IMR-32为体外模型，研究三氧化二砷对人神经母细胞瘤侵袭性生长的影响。从0.5mM开始，As_2O_3呈剂量依赖性抑制IMR-32细胞的增殖。在1.5 mM或更高的浓度下，As_2O_3上调caspase-3的表达，导致细胞凋亡。然而，神经丝-200 kDa和酪氨酸羟化酶并没有上调，这意味着神经元的分化很小。随之而来的是TrkA下调，TrkB上调。蛋白激酶C(PKC)抑制剂Ro-31-8220可部分阻断As_2O_3诱导的细胞凋亡，这意味着As_2O_3可能通过激活PKC来传递信号。结果提示，三氧化二砷可能在神经母细胞瘤中有潜在的应用价值。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
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.