All-trans retinoic acid arrests neuroblastoma cells in a dormant state.: Subsequent nerve growth factor/brain-derived neurotrophic factor treatment adds modest benefit
All-trans retinoic acid arrests neuroblastoma cells in a dormant state.: Subsequent nerve growth factor/brain-derived neurotrophic factor treatment adds modest benefit
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DOI：
10.1016/j.jpedsurg.2008.01.007
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发表时间：
2008-07-01
影响因子：
2.4
通讯作者：
Troebs, Ralf B.
中科院分区：
文献类型：
--
作者：
Cernaianu, Grigore;Brandmaier, Philipp;Troebs, Ralf B.
背景：诱导神经母细胞瘤（NB）分化或凋亡的治疗是一个重要的研究课题。尽管维甲酸显示出有希望的抗肿瘤结果，但其对难治性疾病的作用有限。联合治疗的假定候选物是神经生长因子（NGF; Tebu-Bio/Peprotech，奥芬巴赫，德国）和脑源性神经营养因子（BDNF; Tebu-Bio/Peprotech，奥芬巴赫，德国），因为它们的受体在临床神经母细胞瘤中具有预后临床价值。另一个临床预后因素是许旺细胞的数量。雪旺细胞分泌的物质在体外证明了抗肿瘤能力。本研究的目的是分析是否视黄酸可以提供一个额外的攻击线独立于雪旺细胞和添加剂治疗与神经营养因子受体配体NGF/BDNF赋予额外的benefit.Methods：人SHSY-5 Y NB细胞体外培养。全反式维甲酸（ATRA; Sigma-Aldrich Chemie，Taufkirchen，德国）处理7天（15 μ mol/L ATRA）后，在二甲基噻唑-二苯基四唑溴化物（MTT）试验中NB增殖与消退成比例。对膜联蛋白和碘化丙啶的荧光活化细胞分选仪（FACS）分析确定了凋亡和坏死的程度以及施旺型细胞标志物S100的表达。逆转录聚合酶链反应检测S100 mRNA表达。此外，当ATRA与NGF或BDNF（10，50，100 ng/mL）在ATRA处理7天之前或之后的7天处理组合时，研究对NB增殖的影响。
Background: Therapies aiming at inducing differentiation or apoptosis of neuroblastoma (NB) are an important research topic. Although retinoic acid showed promising antitumoral results, its effects against refractory disease are limited. Putative candidates for combination therapies are nerve growth factor (NGF; Tebu-Bio/Peprotech, Offenbach, Germany) and brain-derived neurotrophic factor (BDNF; Tebu-Bio/Peprotech, Offenbach, Germany) because their receptors are of prognostic clinical value in clinical neuroblastoma. Another clinical prognostic factor is the number of Schwann cells. Substances secreted by Schwann cells proved antitumoral capacities in vitro. The aim of the study was to analyze whether retinoic acid may offer an additional line of attack acting independent from Schwann cells and whether additive treatment with the neurotrophin-receptor ligands NGF/BDNF confers additional benefit.Methods: Human SHSY-5Y NB cells were cultured in vitro. After a 7-day all-trans retinoic acid (ATRA; Sigma-Aldrich Chemie, Taufkirchen, Germany) treatment (15 mu mol/L of ATRA), NB proliferation was proportional to extinction in dimethyl-thiazol-diphenyltetrazoliumbromide (MTT) tests. Fluorescence-activated cell sorter (FACS) analysis for annexin and propidium iodide determined the degree of apoptosis and necrosis as well as the expression of the Schwann type cell marker S100. The S100 messenger RNA was assessed by reverse transcriptase polymerase chain reaction. In addition, the effect on NB proliferation was investigated when ATRA was combined with a 7-day treatment with NGF or BDNF (10, 50, 100 ng/mL) either before or after the 7-day ATRA treatment.