gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, 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

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc286.shtml

Published: May 8, 2006

© 2006 Koschny et al.
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Outline

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.