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

Abstract

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 G0/G1 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 KV or KATP 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.

ATP-Sensitive Potassium Channel Activation Induces Angiogenesis In Vitro and In Vivo

“…The reported growth-related effects of both CNP (Khambata et al, 2011) and of H 2 S (Papapetropoulos et al, 2009) on endothelial cells as well as our present results (Figs. 3 and 4) are indeed compatible with the reported ability of K ATP activators to induce proliferation in a wide variety of cell types, both normal (Fogal et al, 2010) and tumor (Ru et al, 2014). However, it should be noted that the activators' proliferative effect depends on the specific cell type under study (Zuo et al, 2011).…”

Voltage-gated K+ channel blocker quinidine inhibits proliferation and induces apoptosis by regulating expression of microRNAs in human glioma U87-MG cells

“…Voltage-gated K + channel blockers, such as 4-aminopyridine, and tetraethylammonium, have been shown to inhibit cell proliferation and growth of tumor via an arrest in the g 0 /g 1 transition during the cell cycle (7). Quinidine, another commonly used voltage-gated K + channel blocker, can reduce the proliferation of tumor cells, such as human malignant mesothelioma cells and rat c6 glioma cells (8,9).…”

Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis?

“…Xenon is also thought to bind to the Kir6.2 subunit of the adenosine triphosphate-dependent potassium channel, causing cytoskeletal changes that are involved in tumourigenesis and cell migration. 23 …”