Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib.
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.
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.
Zammam
Z
Areeb
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.|Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
Stanley S
SS
Stylli
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.
Thomas M B
TM
Ware
Regenerative Surgery Group, O'Brien Institute Tissue Engineering Centre, Fitzroy, VIC, 3065, Australia.|Department of Plastic and Reconstructive Surgery, St Vincent's Hospital, Fitzroy, VIC, 3065, Australia.
Nicole C
NC
Harris
Regenerative Surgery Group, O'Brien Institute Tissue Engineering Centre, Fitzroy, VIC, 3065, Australia.|Department of Plastic and Reconstructive Surgery, St Vincent's Hospital, Fitzroy, VIC, 3065, Australia.
Lipi
L
Shukla
Regenerative Surgery Group, O'Brien Institute Tissue Engineering Centre, Fitzroy, VIC, 3065, Australia.|Department of Plastic and Reconstructive Surgery, St Vincent's Hospital, Fitzroy, VIC, 3065, Australia.
Ramin
R
Shayan
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.
Lucia
L
Paradiso
Paediatric Neurosurgery, Department of Paediatric Surgery, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, People's Republic of China.|Brain Science Research Institute of Shandong University, Jinan, 250012, People's Republic of China.
Bo
B
Li
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.|Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
Andrew P
AP
Morokoff
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia.|Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
Andrew H
AH
Kaye
Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Level 5, Clinical Sciences Building, Parkville, VIC, 3050, Australia. rluwor@unimelb.edu.au.
Rodney B
RB
Luwor
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000069286:Bortezomib / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D000069286:Bortezomib; C524865:carfilzomib; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Carfilzomib; Glioblastoma multiforme; Invasion; MMP2; Migration; Proteasome