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61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Joint Meeting mit der Brasilianischen Gesellschaft für Neurochirurgie am 20. September 2010

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21. - 25.09.2010, Mannheim

Enhancement of the growth-inhibitory effect of temozolomide by the nitric oxide donor PABA/NO in U87 glioma cells in vitro

Meeting Abstract

Suche in Medline nach

  • Evangelos Kogias - Abteilung für Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland
  • Brunhilde Baumer - Abteilung für Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland
  • Astrid Weyerbrock - Abteilung für Allgemeine Neurochirurgie, Uniklinik Freiburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1716

DOI: 10.3205/10dgnc187, URN: urn:nbn:de:0183-10dgnc1874

Veröffentlicht: 16. September 2010

© 2010 Kogias 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: Resistance to temozolomide, the standard chemotherapy for gliomas in humans, represents an important issue in current therapy schemes. Emerging evidence suggests that nitric oxide may potentially lead to a sensitization of tumor cells to a variety of chemotherapeutic compounds. The nitric oxide donor PABA/NO selectively releases nitric oxide in GST-pi overexpressing glioma cells after enzymatic activation. We tested the hypothesis that PABA/NO may enhance the growth-inhibitory effect of temozolomide in U87 cells in vitro.

Methods: We exposed U87 cells to temozolomide concentrations between 1 µM and 100 µM alone as well as concomitantly with PABA/NO concentrations between 5 µM and 50 µM for 24 h. Viability was assessed after 24 h incubation, as well as 48 h and 72 h after drug removal by MTT assay. Statistical analysis was performed by ANOVA.

Results: The IC50 concentrations for PABA/NO and temozolomide alone were 45 µM and 100 µM, respectively. PABA/NO significantly enhanced the growth-inhibitory effect of temozolomide in U87 glioma cells (p<0.0001). PABA/NO concentrations between 5 and 25 µM which did not have an intrinsic antiproliferative effect alone, lead to a significant increase in temozolomide cytotoxicity. Concomitant treatment of U87 cells with PABA/NO and temozolomide concentrations as low as 1 µM reduced cell viability up to 80%.

Conclusions: The nitric oxide donor PABA/NO significantly enhances the cytotoxic effect of temozolomide in U87 glioma cells in vitro. Using a nitric oxide donor to overcome resistance to temozolomide might be a new strategy to improve the efficacy of multimodal glioma treatment.