Han Ying, Shi Yongquan, Han Zheyi, Sun Li, Fan Daiming
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.
Cell Biol Int. 2007 Jul;31(7):741-7. doi: 10.1016/j.cellbi.2007.01.008. Epub 2007 Jan 21.
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.
本研究旨在探究钾电流,并进一步探讨钾通道在胃癌细胞药物反应中的作用。采用膜片钳技术,以电压钳模式记录人胃癌细胞SGC7901的钾电流。4-氨基吡啶(4-AP)和四乙铵(TEA)均可几乎完全阻断该电流。化疗药物阿霉素或5-氟尿嘧啶可显著以剂量依赖方式增加SGC7901细胞上的K(+)电流密度。发现4-AP或TEA可抑制阿霉素诱导的SGC7901细胞凋亡并增强其多药耐药表型。在包括SGC7901在内的胃癌细胞中广泛表达的Kv1.5上调,增加了SGC7901细胞的K(+)电流密度及其对多种化疗药物的敏感性,而Kv1.5下调则增强了SGC7901细胞的耐药表型。总之,钾通道可能通过调节胃癌细胞中药物诱导的凋亡对多药耐药发挥调节作用。