Effects of Bortezomib on Human Neuroblastoma Cells In Vitro and in a Metastatic Xenograft Model

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 neuroblast...

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Bibliographic Details
Published in:Anticancer research 2009-04, Vol.29 (4), p.1219-1225
Main Authors: VALENTINER, Ursula, HAANE, Christina, NEHMANN, Nina, SCHUMACHER, Udo
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
Biological and medical sciences
Blotting, Western
Boronic Acids - therapeutic use
Bortezomib
Cell Movement - drug effects
Cell Proliferation - drug effects
Female
Humans
Immunoenzyme Techniques
Male
Medical sciences
Mice
Mice, SCID
Mitosis - drug effects
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Neuroblastoma - secondary
Neurology
Pyrazines - therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tumor Cells, Cultured
Tumors
Tumors of the nervous system. Phacomatoses
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0250-7005
1791-7530