coriaria-lactone and Brain-Neoplasms

Hypoxia-inducible factor-1α (HIF-1α) is thought to mediate pharmacoresistance in tumor by inducing Pgp overexpression. We aimed to investigate the expression of HIF-1α and MDR1/P-glycoprotein in refractory epilepsy, to explore the correlation of HIF-1α with epilepsy multidrug resistance. We collected hippocampus and mesial temporal lobe (MTL) cortex of refractory mesial temporal lobe epilepsy (mTLE) patients that underwent surgery, and established a pharmacoresistant TLE rat model kindled by coriaria lactone. We used real-time quantitative PCR (RQ-PCR) and western blot to investigate expression of HIF-1α and MDR1 in hippocampus and MTL/entorhinal cortex. We found that the expression of HIF-1α and MDR1, at both mRNA and protein levels, were up-regulated in hippocampus and MTL cortex of mTLE patients compared with the control cortex (all P < 0.05), and increased in hippocampus and entorhinal cortex of kindled rat model versus the control group (all P < 0.05). These results demonstrated the overexpression of HIF-1α and MDR1/Pgp in hippocampus and MTL/entorhinal cortex of mTLE patients and the pharmacoresistant TLE rat model. HIF-1α may have a regulatory effect on MDR1 expression in refractory epilepsy, which is probably consistent with MDR mechanism in tumor.

Topics: Adult; Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Brain Neoplasms; Case-Control Studies; Cerebral Hemorrhage; Convulsants; Disease Models, Animal; Drug Resistance, Multiple; Entorhinal Cortex; Epilepsy, Temporal Lobe; Female; Genes, MDR; Hippocampus; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kindling, Neurologic; Lactones; Male; Middle Aged; Nerve Tissue Proteins; Random Allocation; Rats; Rats, Sprague-Dawley; Up-Regulation; Young Adult