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Multidrug resistance-associated protein MRP1 expression in
human gliomas: chemosensitization to vincristine and etoposide by indomethacin
in human glioma cell lines overexpressing MRP1
Benyahia B, Huguet S, Decleves X, Mokhtari K, Criniere E, Bernaudin JF,
Scherrmann JM, Delattre JY
Department of Neurology Mazarin (AP-HP) and INSERM U495, Groupe
Hospitalier Pitie-Salpetriere, Paris, France. baya.benyahia@psl.ap-hop-paris.fr
The 190 kDa multidrug resistance protein MRP1 is likely to be involved in the
multidrug resistance phenotype of human gliomas.
MRP1 expression was evaluated in surgical tumor samples from 17 patients with
gliomas.
In addition, the impact of the MRP's inhibitor, indomethacin, on the
chemosensitivity to etoposide (VP16) and vincristine (VCR) of two glioblastoma
cell lines expressing MRP1 (GL15 and 8MG) was investigated.
When evaluated in tumor samples, MRP1 expression was observed in all of them
with more than 90% of stained tumor cells in 14/15 high-grade gliomas.
MRP1 was also strongly expressed at the membrane of the vascular endothelial
cells in the same 14 tumor samples, suggesting that the permeability to
anticancer drugs could be also limited across brain tumor vessels.
At concentrations comprised between 5 and 50 microM, indomethacin significantly
increased the cytotoxic effect of etoposide in both cell lines but it was more
efficient in increasing the cytotoxicity of VCR on GL15 cells, as compared with
8MG cells.
These results suggest that the association of indomethacin to VCR or etoposide
could be of interest in the clinical management of gliomas.
PMID: 15015771 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15015771
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