期刊
EUROPEAN JOURNAL OF CANCER
卷 44, 期 6, 页码 876-884出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2008.02.022
关键词
rhabdomyosarcoma; bortezomib; proteasome; novel cancer therapies
类别
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, divided into two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). To explore the possibility that the proteasome could be a target of therapeutic value in rhabdomyosarcoma, we treated several RMS cell lines with the proteasome inhibitor bortezomib (Velcade or PS-341) at a concentration of 13-26 nM. RMS cells showed high sensitivity to the drug, whereas no toxic effect was observed in primary human myoblasts. In both ERMS and activation of caspase 3 and 7 and induced a ARMS cells bortezomib promoted apoptosis, dose-dependent reduction of anchorage-independent growth. Furthermore, bortezomib induced activation of the stress response, cell cycle arrest and the reduction of NF-kappa B transcriptional activity. Finally, bortezomib decreased tumour growth and impaired cells viability, proliferation and angiogenesis in a xenograft model of RMS. In conclusion, our data indicate that bortezomib could represent a novel drug against RMS tumours. (c) 2008 Elsevier Ltd. All rights reserved.
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