Chen Lei, Cheng Xinwang, Tian Linyu, Yang Tianhua, Hermann Stefan, Zhou Dong
Department of Neurology, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu, Sichuan, China.
Neurochem Res. 2009 Mar;34(3):411-7. doi: 10.1007/s11064-008-9797-3. Epub 2008 Aug 2.
The development of multiple drug resistance (MDR) is a significant problem in epilepsy therapy. The primary factor responsible for antiepileptic drug (AEDs) resistance is the over-expression of the MDR gene product, P-glycoprotein (Pgp). To model a therapeutic approach for decreasing drug resistance in patients with intractable epilepsy, we established a model of coriaria lactone (CL) induced Pgp overexpression in rat astrocytes and administered a recombinant adenovirus Ad5-EGFP-shRNA1-U6 to deliver an anti-mdr1b short hairpin RNA (shRNA) for 5 days. We then investigated the gene-silencing effects of shRNA by quantitative real-time RT-PCR, Western-blot, and Rho123 accumulation assay. The results showed that over-expression of mdr1b and Pgp was successfully suppressed, the ability of intracellular Rho123 retention was increased, and drug efflux was decreased in the adenovirus treated astrocytes. In conclusion, MDR was reversed in rat astrocyte model. These findings may be favorable for developing new therapeutic strategies for treating intractable epilepsy.
