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Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

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Abstract

Glioblastoma multiforme is the most aggressive and lethal tumor of the central nervous system with limited treatment strategies on offer, and as such the identification of effective novel therapeutic agents is paramount. To examine the efficacy of proteasome inhibitors, we tested bortezomib, carfilzomib, nafamostat mesylate, gabexate mesylate and acetylsalicylic acid on glioblastoma cell viability, migration and invasion. Both bortezomib and carfilzomib produced significant reduction of cell viability, while nafamostat mesylate, gabexate mesylate and acetylsalicylic acid did not. Subsequent testing showed that carfilzomib significantly reduced cell viability at nM concentrations. Carfilzomib also reduced cell migration, secretion and activation of MMP2 and also cell invasion of all four glioblastoma cells tested. In summary, carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme.

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Authors and Affiliations

  1. Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia

    Zammam Areeb, Stanley S. Stylli, Thomas M. B. Ware, Lucia Paradiso, Andrew P. Morokoff, Andrew H. Kaye & Rodney B. Luwor

  2. Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia

    Stanley S. Stylli, Andrew P. Morokoff & Andrew H. Kaye

  3. Regenerative Surgery Group, O’Brien Institute Tissue Engineering Centre, Fitzroy, VIC, 3065, Australia

    Nicole C. Harris, Lipi Shukla & Ramin Shayan

  4. Department of Plastic and Reconstructive Surgery, St Vincent’s Hospital, Fitzroy, VIC, 3065, Australia

    Nicole C. Harris, Lipi Shukla & Ramin Shayan

  5. Paediatric Neurosurgery, Department of Paediatric Surgery, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Bo Li

  6. Brain Science Research Institute of Shandong University, Jinan, 250012, People’s Republic of China

    Bo Li

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  1. Zammam Areeb
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Correspondence to Rodney B. Luwor.

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Areeb, Z., Stylli, S.S., Ware, T.M.B. et al. Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib. Med Oncol 33, 53 (2016). https://doi.org/10.1007/s12032-016-0767-3

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