gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit den Benelux-Ländern und Bulgarien

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

24. - 27.05.2009, Münster

Inhibition of vincristine cytotoxicity by blocking glucose transporter 1 in human glioblastoma cell lines

Meeting Abstract

Suche in Medline nach

  • F. Stockhammer - Neurochirurgische Klinik, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin
  • A. Elstner - Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin
  • A. von Deimling - DKFZ und Institut für Neuropathologie, Universität Heidelberg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP14-12

DOI: 10.3205/09dgnc410, URN: urn:nbn:de:0183-09dgnc4109

Veröffentlicht: 20. Mai 2009

© 2009 Stockhammer 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

Text

Objective: Vincristine (VCR) is a widely used cytostatic agent in malignant gliomas. Due to its hydrophilic properties cellular uptake depends on transport. In gliomas this transport has not been studied up to now. However, in other cancers glucose transporter 1 (GLUT1) was identified to accomplish VCR efflux. As GLUT1 is overexpressed in hypoxic glioma regions, the VCR effect was investigated after selective GLUT1 blockage in cultured glioma cell lines.

Methods: U373MG, DBTRG05MG and a primary glioblastoma cell culture (BER) were incubated under hypoxic conditions (1% O2). GLUT1 expression was determined by Western blot analysis. Cell lines were treated either with 1µg/ml VCR for 24 hours alone or in combination with 50µM phloretin, a GLUT1 blocking agent. Furthermore, we investigated the effect of phloretin withdrawal during VCR treatment. The cytotoxic effect was measured by cell counts using a CASY cell counter.

Results: GLUT1 was strongly expressed in all cell lines under hypoxic conditions. VCR led to a significant cell reduction (p<0.001). This cytotoxic effect could be inhibited by addition of phloretin (p<0.001), resulting in almost normal cell growth compared to untreated control samples (p>0.05). Later phloretin removal by washing led to reduced cell growth, too (p<0.01). In all experiments cell size was inversely correlated to cell count.

Conclusions: Blockade of GLUT1 reversibly inhibits vincristine cytotoxicity in cultured glioma cells. GLUT1 could be the major transport gateway for vincristine in gliomas. Further investigations should target GLUT1 to improve the effect of chemotherapy.