College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Gwanak-gu, Seoul 151-742, South Korea.
Eur J Pharmacol. 2011 Jan 25;651(1-3):26-32. doi: 10.1016/j.ejphar.2010.10.066. Epub 2010 Nov 16.
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.
电压门控钾 (Kv) 通道广泛表达于许多细胞的质膜中，在兴奋性神经元细胞和非兴奋性上皮细胞中均参与多种细胞功能。最近已经证明，Kv 通道与多种类型的癌细胞增殖有关。在本研究中，我们研究了抑制 Kv1.3 表达对人肺腺癌 A549 细胞增殖和细胞周期进程的影响。用 margatoxin (MgTX) 处理，MgTX 是 Kv1.3 的选择性阻断剂或 Kv1.3 的短发夹 RNA (shRNA)，可显著阻断 A549 细胞的增殖。此外，Kv1.3 的选择性抑制显著增加了 p21(Waf1/Cip1)的表达水平，并显著降低了 Cdk4 和细胞周期蛋白 D3 的表达水平。我们还将 MgTX 应用于裸鼠的异种移植模型中，并且 MgTX 注入肿瘤组织时会导致肿瘤体积减小。这些结果表明 Kv1.3 可能成为肺腺癌治疗的新的治疗靶点。
