title: Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.
abstract: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer.
  
  
  
  To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux.
  
  
  
  In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway.
  
  
  
  The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Anatomy and Cell Biology, and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea. leeso@snu.ac.kr.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology*; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D024642:Potassium Channels, Voltage-Gated; D011799:Quinazolines; D000077156:Gefitinib
keywords: Combination therapy; Drug resistance; Lung cancer cell; Side population; Voltage-gated potassium channel