去铁胺和羟基吡啶酮对造血祖细胞和神经外胚层肿瘤细胞的作用。

Effect of desferrioxamine and hydroxypyridones on hemopoietic progenitors and neuroectodermal tumor cells.

作者信息

Timeus F, Valle P, Crescenzio N, Ruggieri L, Rosso P, Pagliardi G L, Cordero di Montezemolo L, Gabutti V, Ramenghi U

机构信息

Department of Pediatric Hematology-Oncology, University of Turin, Italy.

出版信息

Am J Hematol. 1994 Nov;47(3):183-8. doi: 10.1002/ajh.2830470307.

DOI:10.1002/ajh.2830470307

PMID:7524314

Abstract

The iron chelator desferrioxamine (DFO) has been shown to inhibit the proliferation of hemopoietic progenitors and several tumor cell lines. We have compared the in viro hemopoietic inhibitory effect of desferrioxamine (DFO) and hydroxypyridones (HPOs) on hemopoietic progenitors and two human neuroectodermal (NE) tumor cell lines, NB 100 and SKNMC. Both DFO and HPOs showed a direct dose-related inhibitory effect on BFU-E and CFU-GM obtained from purified human non-T MNAC (T-lymphocyte-depleted nonadherent mononuclear cells) and CD34+ cells. DFO and HPOs displayed both an inhibitory and a cytotoxic effect on NE cell lines. We calculated the ratio between NE cell and hemopoietic cell growth inhibition for a range of concentrations of chelators. DFO showed the most satisfactory ratio. This suggests that DFO is still the most preferable chelating agent for the treatment of neuroblastoma, since it combines the highest antineuroblastoma effect with the lowest hematopoietic toxicity.

摘要

铁螯合剂去铁胺（DFO）已被证明可抑制造血祖细胞和多种肿瘤细胞系的增殖。我们比较了去铁胺（DFO）和羟基吡啶酮（HPOs）对造血祖细胞以及两种人神经外胚层（NE）肿瘤细胞系NB 100和SKNMC的体外造血抑制作用。DFO和HPOs对从纯化的人非T MNAC（T淋巴细胞去除的非贴壁单核细胞）和CD34 +细胞中获得的BFU-E和CFU-GM均表现出直接的剂量相关抑制作用。DFO和HPOs对NE细胞系均显示出抑制作用和细胞毒性作用。我们计算了一系列螯合剂浓度下NE细胞与造血细胞生长抑制之间的比率。DFO显示出最令人满意的比率。这表明DFO仍是治疗神经母细胞瘤最优选的螯合剂，因为它将最高的抗神经母细胞瘤作用与最低的造血毒性结合在一起。