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

The tetracyclic antibiotic doxycyline downregulates MMP-expression in glioma cells in vitro and inhibts cell migration, proliferation and invasion

Das tetrazyklische Antibiotikum Doxycyclin inhibiert die MMP-Expression in Gliomzellen in-vitro und reduziert Zellmigration, Proliferation und Invasion

Meeting Abstract

  • corresponding author M. Meinhardt - Neurochirurgische Klinik und Poliklinik der Universität Würzburg
  • K. Dette - Neurochirurgische Klinik und Poliklinik der Universität Würzburg
  • C. Herbold - Neurochirurgische Klinik und Poliklinik der Universität Würzburg
  • G. H. Vince - Neurochirurgische Klinik und Poliklinik der Universität Würzburg
  • K. Roosen - Neurochirurgische Klinik und Poliklinik der Universität Würzburg

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. DocP151

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0419.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Meinhardt 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

The antiproliverative and antiinvasive effect of chemically modified tetracyclines (CMT) on prostate tumor cells has been shown in recent studies. CMT are also potent inhibitors of Matrix Metalloproteases (MMPs). We examined the effect of doxycycline (DC) on the cellbiological characteristics, proliferation and migration of glioma cell lines and primary cultures.

Methods

The human glioma cell lines GaMG, U251, U373 and 5 additional primary cell cultures from patients with glioblastoma disease were treated with DC (1,5 ug/ml). Characteristics of treated cells were investigated by MTT-proliferation test, spheroid drop migration, amido-black adhesion assay and 3-D collagen gel invasion test. Semiquantiataive PCR at m RNA level and immunochemistry at protein level were used to detect expression levels of MMP-2, MMP-9 and TIMP-1. Additional routine and apoptosis stains were prepared.

Results

The proliferative activity of DC treated cells was decreased (Cell lines 38%- primary cultures 27%). 3-D Invasion in primary cultures was reduced by 48% and migration by 20% on the average. In general, the effect on primary cultures was more marked than the effect on cell lines. Lower expression levels of MMP-2- and MMP-9-protein were displayed by treated cells. In immunhistochemistry the level of TIMP-1 was unchanged. The results were confirmed at mRNA level by semiquantitative PCR.

Conclusions

The tetracyclic antibiotic is a powerful inhibitor of proliferation and migration of glioma cells in vitro. It works as an inhibitor of matrix metalloproteases even when used at therapeutic plasma concentration. Gelatinase A and B seem to be the main targets of DC to inhibit migration and invasion. The in vitro data in glioma cell lines and primary cultures support similar data in other tumor entities and warrant further investigation of the clinical potential of CMT in patients with gliomatous disease.