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硼替佐米对人神经母细胞瘤细胞的体外及转移异种移植模型的作用。

Effects of bortezomib on human neuroblastoma cells in vitro and in a metastatic xenograft model.

作者信息

Valentiner Ursula, Haane Christina, Nehmann Nina, Schumacher Udo

机构信息

University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.

出版信息

Anticancer Res. 2009 Apr;29(4):1219-25.

PMID:19414367
Abstract

BACKGROUND

Inhibition of the proteasome-ubiquitin pathway has shown to exert growth inhibitory effects on several human carcinoma cell lines. In this study, the influence of bortezomib on human neuroblastoma cells was investigated.

MATERIALS AND METHODS

Cell proliferation of seven human neuroblastoma cell lines under bortezomib treatment was assessed by a colorimetric XTT-based assay. Subsequently, the influence of bortezomib on SK-N-SH neuroblastoma cell growth was examined in a spontaneous metastatic SCID mouse model.

RESULTS

In vitro, bortezomib inhibited proliferation of all cell lines in a dose-dependent manner. In the xenograft model, bortezomib treatment did not have an effect on the tumour weight, but induced apoptosis and reduced mitosis and angiogenesis, as well as the formation of pulmonary metastases.

CONCLUSION

Bortezomib has anticancer effects on neuroblastoma cells in vitro and in a metastatic xenograft model. These findings provide a basis for further investigations of bortezomib in the treatment of metastasising neuroblastoma.

摘要

背景

蛋白酶体-泛素途径的抑制已显示对多种人类癌细胞系具有生长抑制作用。在本研究中,研究了硼替佐米对人神经母细胞瘤细胞的影响。

材料与方法

通过基于比色XTT的检测法评估硼替佐米处理下七种人神经母细胞瘤细胞系的细胞增殖。随后,在自发转移的SCID小鼠模型中检测硼替佐米对SK-N-SH神经母细胞瘤细胞生长的影响。

结果

在体外,硼替佐米以剂量依赖的方式抑制所有细胞系的增殖。在异种移植模型中,硼替佐米处理对肿瘤重量没有影响,但可诱导细胞凋亡并减少有丝分裂和血管生成,以及肺转移的形成。

结论

硼替佐米在体外和转移异种移植模型中对神经母细胞瘤细胞具有抗癌作用。这些发现为进一步研究硼替佐米治疗转移性神经母细胞瘤提供了基础。

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