Voltage- gated and ATP- sensitive K plus channels are associated with cell proliferation and tumorigenesis of human glioma

Increasing evidence indicates that potassium (K+) channels play important roles in the growth and development of human cancer. In the present study, we investigated the contribution of and the mechanism by which K+ channels control the proliferation and tumor development of U87-MG human glioma cells. A variety of K+ channel blockers and openers were used to differentiate the critical subtype of K+ channels involved. The in vitro data demonstrated that selective blockers of voltage-gated K+ (K-V) channels or ATP-sensitive K+ (K-ATP) channels significantly inhibited the proliferation of U87-MG cells, blocked the cell cycle at the G(0)/G(1) phase and induced apoptosis. In the U87-MG xenograft model in nude mice, K-V or K-ATP channel blockers markedly suppressed tumor growth in vivo. Furthermore, electrophysiological results showed that K-V or K-ATP channel blockers inhibited K-V/K-ATP channel currents as well as cell proliferation and tumor growth over the same concentration range. In contrast, iberiotoxin, a selective blocker of calcium-activated K+ channels, had no apparent effect on the cell proliferation, cell cycle or apoptosis of U87-MG cells. In addition, the results of fluorescence assays indicated that blockers of K-V or K-ATP channels attenuated intracellular Ca2+ signaling by blocking Ca2+ influx in U87-MG cells. Taken together, these data suggest that K-V and K-ATP channels play important roles in the proliferation of U87-MG cells and that the influence of K-V and K-ATP channels may be mediated by a Ca2+-dependent mechanism.