Anti‐proliferative Effect of Kv1.3 in A549 Human Lung Adenocarcinoma in vitro and in vivo

Abstract

Voltage‐gated potassium channels (Kv) 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 suppressed expression of Kv1.3 on cell proliferation and cell cycle distribution in human lung adenocarcinoma, A549 cells. Treatment with margatoxin (MgTX), a selective blocker of Kv1.3, and shRNA against Kv1.3, significantly blocked A549 cell proliferation. In addition, selective inhibition of Kv1.3 significantly increased expression level of p21Waf1/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 tumor tissues. These results suggest that Kv1.3 may serve as a novel therapeutic target for lung adenocarcinoma therapy. This work is supported by National Research Foundation of Korea (2009‐0066580)