title: Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo.
abstract: 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.
authors.affiliation: College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Gwanak-gu, Seoul 151-742, South Korea.
authors.forename: Soo Hwa
authors.initials: SH
authors.lastname: Jang
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D055029:Inverted Repeat Sequences; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics*; D012604:Scorpion Venoms / Q000494:pharmacology
chemical_list: D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering; D012604:Scorpion Venoms; C077910:margatoxin