The vitamin A analogues:: 13-cis retinoic acid, 9-cis retinoic acid, and Ro 13-6307 inhibit neuroblastoma tumour growth in vivo
The vitamin A analogues:: 13-cis retinoic acid, 9-cis retinoic acid, and Ro 13-6307 inhibit neuroblastoma tumour growth in vivo
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DOI：
10.1002/1096-911x(20010101)36:1
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Kogner, P
中科院分区：
文献类型：
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作者：
Ponthan, F;Borgström, P;Kogner, P
背景神经母细胞瘤是一种儿童交感神经系统肿瘤，在不接受或接受最低限度的治疗后，可能会因细胞凋亡而自发分化或消退。然而，大多数神经母细胞瘤被诊断为转移性肿瘤，尽管进行了密集的多模式治疗，但预后不良。维生素A及其类似物（视黄酸，RA）在正常细胞分化和程序性细胞死亡中起重要作用。RA在体外调节神经母细胞瘤的生长和分化，并在体内显示出对人神经母细胞瘤的活性。最近，9-顺式RA显示出在体外使用5天短期治疗和随后的洗脱诱导神经母细胞瘤的细胞凋亡。在本研究中，采用连续或短期方案，用13-cis RA（每日4 mg po）、9-cis RA（每日5 mg po）或新型类似物Ro 13-6307（每日0.3 mg po）治疗具有人神经母细胞瘤SH-SY 5 Y异种移植物的裸大鼠。结果与未处理的对照组相比，所有三种不同的类维生素A在8-12天后显著降低神经母细胞瘤生长的肿瘤重量（P < 0.05）。在13-顺式RA处理的大鼠中观察到轻微的毒性体征。然而，在用9-顺式RA和Ro 13-6307处理的所有大鼠中观察到严重毒性和显著体重减轻。连续给药方案的毒性更明显。结论，我们得出结论，不同的维甲酸减少神经母细胞瘤在体内的肿瘤生长。给药方案和剂量可能影响疗效和毒副作用。进一步的体内研究是必要的，包括药代动力学和分子分析，在临床试验之前，有前途的类维生素A如9-顺式RA和Ro 13-6307可以开始在儿童神经母细胞瘤。儿科医学Oncol. 36：127-131，2001. (C)2001 Wiley-Liss，Inc.
Background. Neuroblastoma, a childhood tumour of the sympathetic nervous system, may undergo spontaneous differentiation or regression due to apoptosis after no or minimal therapy. However, the majority of neuroblastomas are diagnosed as metastatic tumours with a poor prognosis in spite of intensive multimodal therapy. Vitamin A and its analogues (retinoic acid, RA) play an important role in normal cellular differentiation and programmed cell death. RA regulates neuroblastoma growth and differentiation in vitro, and has shown activity against human neuroblastoma in vivo. Procedure, Recently, 9-cis RA was shown to induce apoptosis in vitro in neuroblastoma using a 5 days short-term treatment and subsequent washout. In the present study, nude rats with human neuroblastoma SH-SY5Y xenografts were treated with 13-cis RA (4 mg po daily), 9-cis RA (5 mg po daily) or the novel analogue Ro 13-6307 (0.3 mg po daily) using either a continuous or short-term schedule. Results. All three different retinoids decreased neuroblastoma growth significantly in terms of tumour weight after 8-12 days when compared to untreated controls (P < 0.05). Minor signs of toxicity in 13-cis RA treated rats were observed. However, severe toxicity with significant weight loss was seen in all rats treated with 9-cis RA and Ro 13-6307. Toxicity was more pronounced with the continuous regimen. Conclusions, We conclude that different retinoids reduce neuroblastoma tumour growth in vivo. Drug scheduling and dosage may affect both therapeutic efficacy and toxic side effects. Further in vivo studies are warranted, including pharmacokinetic and molecular analyses, before clinical trials with promising retinoids like 9-cis RA and Ro 13-6307 can be started in children with neuroblastoma. Med. Pediatr. Oncol. 36:127-131, 2001. (C) 2001 Wiley-Liss, Inc.