title: Detection of potassium currents and regulation of multidrug resistance by potassium channels in human gastric cancer cells.
abstract: The present study aimed to investigate the potassium currents and further explore the role of potassium channels in drug response of gastric cancer cells. By patch-clamp technique, potassium currents of human gastric cancer cell SGC7901 were recorded in the mode of voltage clamp. Both 4-aminopyridine (4-AP) and tetraethylammonium (TEA) could almost completely block this current. The chemotherapeutic drugs, adriamycin or 5-fluorouracil could significantly increase the K(+) current density on SGC7901 cells in a dose-dependent manner. 4-AP or TEA was found to restrain adriamycin-induced apoptosis and enhance multidrug-resistant phenotype of SGC7901 cells. Up-regulation of Kv1.5, which has been found widely expressed in gastric cancer cells including SGC7901, increased the K(+) current density and sensitivity of SGC7901 cells to multiple chemotherapeutic drugs, whereas down-regulation of Kv1.5 enhanced the drug-resistant phenotype of SGC7901 cells. In conclusion, potassium channels may exert regulatory effects on multidrug resistance by regulating drug-induced apoptosis in gastric cancer cells.
authors.affiliation: Department of Gastroenterology, State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an 710032, Shaanxi Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Zheyi
authors.initials: Z
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
chemical_list: C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D004317:Doxorubicin; D011188:Potassium