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

Ru,Qin; Tian,Xiang; Wu,Yu-Xiang; Wu,Ri-Hui; Pi,Ming-Shan; Li,Chao-Ying

doi:10.3892/or.2013.2875

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

Authors:
- Qin Ru
- Xiang Tian
- Yu-Xiang Wu
- Ri-Hui Wu
- Ming-Shan Pi
- Chao-Ying Li
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Affiliations: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China
Published online on: November 27, 2013 https://doi.org/10.3892/or.2013.2875
Pages: 842-848

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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+ (KV) channels or ATP-sensitive K+ (KATP) 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, KV or KATP channel blockers markedly suppressed tumor growth in vivo. Furthermore, electrophysiological results showed that KV or KATP channel blockers inhibited KV/KATP 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 KV or KATP channels attenuated intracellular Ca2+ signaling by blocking Ca2+ influx in U87-MG cells. Taken together, these data suggest that KV and KATP channels play important roles in the proliferation of U87-MG cells and that the influence of KV and KATP channels may be mediated by a Ca2+-dependent mechanism.

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