title: 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.
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ru
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Wu
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Ri-Hui
authors.initials: RH
authors.lastname: Wu
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Pi
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Li
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005910:Glioma; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors*; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D054086:KATP Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; D003981:Diazoxide; D010693:Phloretin; D005905:Glyburide; D002118:Calcium