XXXX resistance in human @entity43 cells.

@entity43 @entity5568 @entity137 @entity5 @entity53783 @entity900 @entity2 @entity898 @entity15337 @entity14688 @entity1435
PURPOSE: This study was performed to determine whether or not in @entity43 cell lines, free radicals (ROS) play a role in @entity900 @entity137 and activation of the mitochondrial and JNK/ @entity1435 pathways. The role of the enzyme, @entity53783 dehydrogenase ( @entity15337 ), in the activation/deactivation of this pathway and how this may be related to the development of resistance was also investigated. METHODS: Mitochondrial membrane potential and ROS analysis were performed by flow cytometry, P-JNK and P- @entity1435 by western blotting and mRNA by RT-PCR. @entity53783 dehydrogenase ( @entity15337 ) and @entity14688 knockdowns were prepared by standard techniques. RESULTS: @entity900 treatment of a cervical @entity5 cell line resulted in ROS production with mitochondrial membrane depolarization and phosphorylation of JNK and @entity1435 . @entity898 , a free radical scavenger, ameliorated these effects. Treatment of the sensitive cells with @entity5568 produced similar effects but at shorter incubation times. Similar results were observed with an ovarian cell line. Downregulation of @entity53783 dehydrogenase in the @entity900 -resistant cervical and @entity2 cell lines resulted in increased drug sensitivity with detectable production of ROS and activation of the JNK/ @entity1435 pathways; however, downregulation of @entity14688  in the cervical cells had minimal effect. CONCLUSION: @entity53783 dehydrogenase appears to play a role in @entity900 resistance in @entity43 cells which includes mitochondrial membrane depolarization, ROS production and activation of the JNK pathway. However, its mode of action cannot be mimicked by an ROS scavenger so its mechanism of action is more complex (a not unexpected finding considering its role in xenobiotic activation/countering oxidative stress).
