Suppression of the multidrug transporter P-glycoprotein using RNA interference in cultured rat astrocytes induced by coriaria lactone.
The overexpression of the multidrug resistance gene (MDR-1) and its translational product p-glycoprotein (P-gp) may play an important role in pharmacoresistant epilepsy. We established the rat astrocyte model overexpressing P-gp induced by coriaria lactone and successfully nucleofected it with the siRNA-hairpin expression vector pSIREN-shuttle designed to target MDR-1B mRNA. The mRNA expression of MDR-1B gene was mostly knock down by 67.70% (p<0.01). The expression of P-gp in experimental group was significantly lower than that in negative control (p<0.05), and the rhodamine efflux ratio of experimental group (23.08%) was remarkably lower than that of negative control (78.35%, p<0.01). We first employed RNA interfering to the drug resistance reversal of refractory epilepsy and this may provide a new way for refractory epilepsy remedy.
Yang
Tian-Hua
TH
Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Tian
Lin-Yu
LY
Shang
Hui-Fang
HF
Cheng
Xin-Wang
XW
Geng
Jia
J
Chen
Lei
L
Zhou
Dong
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D019450:Genes, MDR / Q000235:genetics*; D007150:Immunohistochemistry; D055029:Inverted Repeat Sequences; D007783:Lactones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007783:Lactones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C049836:coriaria lactone