Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells.
Ion movements are among the early signals that could play important roles in cancer cell proliferation and metastasis. In this work, we investigated the role of K+ channels in adhesion and proliferation of H35 hepatocarcinoma cells. A variety of K+ channel blockers were used in order to differentiate the critical subtype(s) of K+ channels involved. 4-Aminopyridine, an inhibitor of voltage-gated K+ channels, significantly reduced the attachment of H35 cells to primary rat endothelial layer as determined by CFSE (5-(6-)-carboxyfluorescein diacetate succinimidyl ester) fluorescence assay. 4-Aminopyridine also inhibited the proliferation of H35 cells as measured by [3H]-thymidine incorporation. Non-selective K+ channel blockers TPeA and verapamil had similar inhibitory effects on H35 cell adhesion and proliferation. In contrast, iberiotoxin, a selective inhibitor of KCa channels, had no effect on the adhesion and proliferation of H35 cells. Glibenclamide, a potent inhibitor of KATP channels, could inhibit the cell adhesion and proliferation only at a very high concentration (100 micro M) that may block Kv channels. These experiments suggest that Kv channels play an important role in the metastasis and proliferation of hepatocarcinoma cells. Since inhibition of K+ channels would reduce Ca2+ influx in these cells, it is likely that the influence of Kv channels on H35 cell adhesion and proliferation is mediated by a Ca2+-dependent mechanism.
Zhou
Qing
Q
Department of Biotechnology, Faculty of Life Science, Zhejiang University, Hangzhow, P.R. China.
Kwan
Hiu-Yee
HY
Chan
Hsiao-Chang
HC
Jiang
Jian-Li
JL
Tam
Siu-Cheung
SC
Yao
Xiaoqiang
X
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D002118:Calcium