Multidrug resistance proteins expression in glioma patients with epilepsy
- 457 Downloads
Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-π (GST-π) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-π in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-π predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.
KeywordsMultidrug resistance Epilepsy Glioma Pgp MRP1 MRP3 GST-π
We thank Dr. E. Ciusani, Dr. C. Vasco and Dr. G. Bedini of Laboratory of Clinical Pathology and Medical Genetics, Fondazione IRCCS Istituto Neurologico “C. Besta”, for their helpful collaboration in western blot analysis.
Conflicts of interest
The authors declare that they have no conflict of interest.
- 7.Calatozzolo C, Gelati M, Ciusani E, Sciacca FL, Pollo B, Cajola L, Marras C, Silvani A, Vitellaro-Zuccarello L, Croci D, Boiardi A, Salmaggi A (2005) Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neurooncol 74(2):113–121. doi: 10.1007/s11060-004-6152-7 PubMedCrossRefGoogle Scholar
- 16.Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Löscher W (2007) Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 52(2):333–346. doi: 10.1016/j.neuropharm.2006.07.038 PubMedCrossRefGoogle Scholar