Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats

This study was performed to investigate the mechanism of the blood–brain tumor-barrier (BTB) permeability increase, which was induced by NS1619, a selective KCa channel activator. Using a rat brain glioma (C6) model, we exam the expression of ZO-1 and occludin in mRNA and protein level at different time point after intracarotid infusion of NS1619 (30 μg/kg/min) to tumor sites via RT-PCR and Western blot analysis. The mRNA and protein expression of ZO-1 and occludin had no great change before infusion and began to decrease significantly after 2 h NS1619 infusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of BTB permeability and malonaldehyde (MDA) level induced by NS1619. This led to the conclusion that NS1619 could time-dependently increase the BTB permeability by down-regulating the expression of tight junction protein, and this effect could be reversed by ROS.

Research highlights
► NS1619 down-regulated the expression of tight junction protein.
► MPG significantly inhibited the increase of BTB permeability induced by NS1619.
► MPG attenuated the effect of NS1619 on tight junction protein.