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.


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.


CONCLUSIONS
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.
Valentiner
Ursula
U
University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. valentin@uke.uni-hamburg.de
Haane
Christina
C
Nehmann
Nina
N
Schumacher
Udo
U
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008938:Mitosis / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D011719:Pyrazines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D012333:RNA, Messenger; D000069286:Bortezomib