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Eur J Cancer. 2008 Apr;44(6):876-84. doi: 10.1016/j.ejca.2008.02.022. Epub 2008 Mar 14.

Bortezomib-mediated proteasome inhibition as a potential strategy for the treatment of rhabdomyosarcoma.

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Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino, Italy.


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 ARMS cells bortezomib promoted apoptosis, activation of caspase 3 and 7 and induced a dose-dependent reduction of anchorage-independent growth. Furthermore, bortezomib induced activation of the stress response, cell cycle arrest and the reduction of NF-kappaB 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.

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