gms | German Medical Science

67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12. - 15. Juni 2016, Frankfurt am Main

The nitric oxide donor JS-K modulates the migration activity of human glioblastoma cells in vitro

Meeting Abstract

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  • Louisa Wolf - Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Germany
  • Nadja Osterberg - Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Germany
  • Astrid Weyerbrock - Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocP 014

doi: 10.3205/16dgnc389, urn:nbn:de:0183-16dgnc3891

Veröffentlicht: 8. Juni 2016

© 2016 Wolf et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

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Objective: Glioblastoma multiforme (GBM) is characterized by a strong and diffuse infiltration of the surrounding brain tissue. By that, some GBM cells might escape anti-tumor treatment and cause secondary tumors even in distant brain areas. Adjuvants targeting tumor cell migration might support multimodal therapy. The diazeniumdiolate JS-K releases nitric oxide (NO) in gluthatione-S-transferase overexpressing GBM cells. JS-K is known to exert anti-invasive effects in breast cancer cells. The aim of this study was to investigate the effect of low dose JS-K on the migration activity of GBM cells and to explore the possible molecular pathways in vitro.

Method: GBM cell lines U87 and T98G as well as primary human GBM cells (IC) were used as cell culture model. Cells were treated with 0-3 µM JS-K over 4 h. Afterwards, the migration capacity was examined by cell motility assays, cytotoxic and anti-proliferative effects of JS-K on GBM cells were analyzed by MTT and BrdU incorporation assays (0-96 h), respectively. Changes in the expression of matrix metalloproteinases (MMP) 2, 7, and 9 and of tissue inhibitor metalloproteinases (TIMP) 1 - 4 induced by JS-K were assessed by Polymerase Chain Reaction (PCR) and Western blot analysis. JS-K dependent effects on MMP 2/7/9 activity were analyzed by zymography and S-nitrosylation status determination by Western blot. Statistical analysis was performed by student’s t-test.

Results: Neither cell viability nor proliferation activity of GBM cells was influenced by JS-K in low concentrations. In contrast, a significant reduction in migration activity by concentrations ≥2 µM JS-K was detectable, most prominently after 96 h. However, expression of MMP 2, 7, and 9 and TIMP 1 - 4 was not affected by JS-K as shown by PCR and Western blot. Zymography demonstrated only a reduced MMP-2 activity by NO after 48 h. This inhibition was independent of protein-S-nitrosylation by JS-K.

Conclusions: JS-K reduces GBM cell migration significantly at low doses predominantly via the inhibition of MMP 2. This makes JS-K a promising candidate as adjuvant in the multimodal GBM therapy reducing invasion of tumor surrounding tissue and, by that, might reduce the risk of tumor recurrence.