gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. bis 14.05.2006, Essen

The proteasome inhibitor Bortezomib sensitizes primary glioblastoma multiforme cells for TRAIL-induced apoptosis

Der Proteasomeninhibitor Bortezomib sensitiviert primäre Glioblastomzellen für TRAIL-induzierte Apoptose

Meeting Abstract

  • corresponding author R. Koschny - Dept. of Apoptosis Regulation, German Cancer Research Center (DKFZ), Heidelberg
  • H. Holland - Biotechnical-Biomedical Centre (BBZ), Faculty of Medicine, University of Leipzig
  • W. Krupp - Clinic of Neurosurgery, University of Leipzig
  • T.L. Haas - Dept. of Apoptosis Regulation, German Cancer Research Center (DKFZ), Heidelberg
  • J. Sykora - Dept. of Apoptosis Regulation, German Cancer Research Center (DKFZ), Heidelberg
  • T.G. Ganten - Dept. of Apoptosis Regulation, German Cancer Research Center (DKFZ), Heidelberg
  • P. Ahnert - Biotechnical-Biomedical Centre (BBZ), Faculty of Medicine, University of Leipzig
  • H. Walczak - Dept. of Apoptosis Regulation, German Cancer Research Center (DKFZ), Heidelberg
  • J. Meixensberger - Clinic of Neurosurgery, University of Leipzig

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 05.69

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2006/06dgnc286.shtml

Veröffentlicht: 8. Mai 2006

© 2006 Koschny et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel cytokine with potent anti-tumor activity. Proteasome inhibition by Bortezomib treatment has been shown to sensitize glioblastoma cell lines for TRAIL-induced apoptosis. So far, the effectiveness of this combinatorial treatment has not been confirmed in primary human glioma cells. The aim of the present study was to investigate the anti-tumor potential of the combinatorial treatment of TRAIL and Bortezomib (PS-341, Valvade®) in primary human glioblastoma cells.

Methods: Primary tumor cells were isolated from freshly operated surgical glioblastoma specimens and cultured in vitro. Passage one cells were treated with Bortezomib and recombinant human TRAIL. Cell death was measured by PI exclusion. Apoptosis was confirmed by Hoechst 33342 stain. In parallel TRAIL receptor expression levels were measured after sensitization with Bortezomib by flow cytometry (FACS).

Results: Primary glioblastoma multiforme cells did not or only very weekly express either of the death inducing TRAIL receptors, TRAIL-R1 or TRAIL-R2. Accordingly, passage one glioblastoma cells were completely resistant for TRAIL-induced apoptosis but could be sensitized for TRAIL by subtoxic doses of Bortezomib. FACS analysis demonstrated a significant up regulation of TRAIL-R2 surface expression upon Bortezomib treatment, thereby explaining the synergistic effect of Bortezomib and TRAIL.

Conclusions: The combinatorial administration of Bortezomib and TRAIL could represent a novel and promising therapeutic option for the treatment of glioblastoma multiforme.