Detection of potassium currents and regulation of multidrug resistance by potassium channels in human gastric cancer cells.
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.
Han
Ying
Y
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.
Shi
Yongquan
Y
Han
Zheyi
Z
Sun
Li
L
Fan
Daiming
D
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
C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D004317:Doxorubicin; D011188:Potassium