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Inhibition of P-glycoprotein Over-expression by shRNA-mdr1b in Rat Astrocytes

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Abstract

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.

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Acknowledgements

This work was supported by the Country natural science foundation (30770749/c030307) and West China Hospital. We are grateful to thank Prof. Sheng-Fu Li, and postgraduate students Zhaoyang Ye and Lizhong Liu for technical assistance.

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Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu, Sichuan, China

    Lei Chen, Xinwang Cheng, Linyu Tian, Tianhua Yang & Dong Zhou

  2. Department of Neurology, Center of Epilepsy (ZEE), University of Erlangen-Nuremberg, Erlangen, Germany

    Stefan Hermann

Authors
  1. Lei Chen
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  2. Xinwang Cheng
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  3. Linyu Tian
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  4. Tianhua Yang
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  5. Stefan Hermann
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  6. Dong Zhou
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Correspondence to Dong Zhou.

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Chen, L., Cheng, X., Tian, L. et al. Inhibition of P-glycoprotein Over-expression by shRNA-mdr1b in Rat Astrocytes. Neurochem Res 34, 411–417 (2009). https://doi.org/10.1007/s11064-008-9797-3

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  • DOI: https://doi.org/10.1007/s11064-008-9797-3

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