gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Modulation of Carboplatin chemotherapy and cytotoxicity of the nitric oxide donor Spermine-NO in glioma cells in vitro

Modulation einer Carboplatin-Chemotherapie und zytotoxische Wirkung des Stickstoffmonoxiddonors Spermine-NO in Gliomzellen in-vitro

Meeting Abstract

Suche in Medline nach

  • corresponding author A. Weyerbrock - Abteilung Allgemeine Neurochirurgie, Neurochirurgische Universitätsklinik Freiburg
  • B. Baumer - Abteilung Allgemeine Neurochirurgie, Neurochirurgische Universitätsklinik Freiburg
  • A. Papazoglou - Abteilung Stereotaktische Neurochirurgie, Neurochirurgische Universitätsklinik Freiburg

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP152

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0420.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Weyerbrock 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

Nitric oxide(NO) and related substances have multiple cytotoxic, chemo- and radiosensitizing effects and are implicated in the regulation of vascular permeability and blood flow. Furthermore, we recently published that concomitant i.v. administration of the NO donor Proli/NO and Carboplatin lead to long-term survival in rats harbouring intracranial C6 gliomas. The objective of this study was to investigate the cytotoxicity of the NO donor Spermine-NO and its potential synergistic effect with Carboplatin in C6, U87 and in human glioblastoma (GBM) cells in vitro.

Methods

Rat C6, human U87 and GBM cells derived from a patient glioblastoma were cultured in a standardized manner and then incubated with Spermine-NO at doses in the range from 10-12 M to 10-2 M for 24, 36 or 48h. Cytotoxicity of Carboplatin was evaluated at concentrations between 500 µM and 2 mM. Furthermore, the cells were simultaneously exposed to Spermine-NO and Carboplatin or each substance alone. Cell viability (%) was calculated after trypan blue dye exclusion assay and cell viability were analysed statistically using ANOVA test and Student´s Newman Keul test.

Results

Exposure of C6, U87 and GBM cells to Spermine-NO at concentrations ≥10-4 M was directly cytotoxic. In C6 cells, addition of Spermine-NO (10-4 M) to the Carboplatin (500 µM) incubation over 36h significantly enhanced cytotoxicity of the drug (52±13% of viable cells (Carboplatin) vs. 65±37% (Spermine-NO) vs. 26±5% (Spermine-NO+Carboplatin); p=0.0006). Similar results were obtained in GBM cells combining 500 µM Carboplatin and 5x10-4 M Spermine-NO after a 48h incubation (p=0.0038). While Spermine-NO and Carboplatin were both significantly cytotoxic in U87 cells, no synergistic effects between these two substances could be observed in this cell line.

Conclusions

Therefore we conclude that Spermine-NO is intrinsically cytotoxic in all three cell lines and has a potent chemosensitizing effect in combination with Carboplatin in C6 and GBM cells. Using these synergistic effects of NO and Carboplatin might be a new strategy to improve the efficacy of chemotherapy for gliomas.