Cheung William M W, Chu Patrick W K, Kwong Yok L
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Cancer Lett. 2007 Feb 8;246(1-2):122-8. doi: 10.1016/j.canlet.2006.02.009. Epub 2006 Mar 29.
A human neuroblastoma cell line, IMR-32, was used as an in vitro model system to study the effects of arsenic trioxide (As(2)O(3)) on aggressive human neuroblastoma. From 0.5 micro M, As(2)O(3) exhibited a dose-dependent inhibition of IMR-32 proliferation. At concentrations of 1.5 micro M or higher, As(2)O(3) 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 down-regulated and TrkB up-regulated. Pre-treatment with the protein kinase C (PKC) inhibitor Ro-31-8220 partially blocked As(2)O(3)-mediated apoptosis, meaning that As(2)O(3) might signal through PKC activation. The results suggest that As(2)O(3) might be potentially useful in neuroblastoma.
一种人神经母细胞瘤细胞系IMR - 32被用作体外模型系统，以研究三氧化二砷（As₂O₃）对侵袭性人神经母细胞瘤的影响。从0.5微摩尔开始，As₂O₃对IMR - 32细胞增殖表现出剂量依赖性抑制。在1.5微摩尔或更高浓度时，As₂O₃上调半胱天冬酶3，导致细胞凋亡。然而，200 kDa神经丝蛋白和酪氨酸羟化酶未上调，这意味着神经元分化程度极低。同时，TrkA下调而TrkB上调。用蛋白激酶C（PKC）抑制剂Ro - 31 - 8220预处理可部分阻断As₂O₃介导的凋亡，这表明As₂O₃可能通过PKC激活来传递信号。结果表明，As₂O₃在神经母细胞瘤治疗中可能具有潜在用途。
