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 µM) 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.
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Document Type: Research Article
Affiliations: Department of Biotechnology, Faculty of Life Science, Zhejiang University, Hangzhow, P.R. China
Publication date: January 1, 2003
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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