Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 651, Issue 1-3, Pages 26-32Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2010.10.066
Keywords
Voltage-gated K channel; Cell proliferation; Cell cycle progression; G1-S transition; Margatoxin; shRNA
Categories
Funding
- National Research Foundation [2010-0011556]
- National Research Foundation of Korea [2010-0011556] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Voltage-gated potassium (Kv) channels are widely expressed in the plasma membranes of numerous cells and contribute to a variety of cellular functions in both excitable neuronal cells and non-excitable epithelial cells. Recently, it has been demonstrated that Kv channels are associated with the proliferation of several types of cancer cells. In the present study, we investigated the effects of suppression of Kv1.3 expression on cell proliferation and cell cycle progression in human lung adenocarcinoma. A549 cells. Treatment with margatoxin (MgTX), a selective blocker of Kv1.3 or short hairpin RNA (shRNA) against Kv1.3, significantly blocked A549 cells' proliferation. In addition, selective inhibition of Kv1.3 significantly increased expression level of p21(Waf1/Cip1) and significantly decreased the expression level of Cdk4 and cyclin D3. We also applied the MgTX into a xenograft model using nude mice, and MgTX caused a reduction of tumor volume when it was injected into the tumor tissues. These results suggest that Kv1.3 may serve as a novel therapeutic target for lung adenocarcinoma therapy. (c) 2010 Elsevier B.V. All rights reserved.
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