【摘要】 目的　探讨 4 氨基吡啶 (4 AP)对小细胞肺癌 (SCLC)中电压激活性K+ 电流和细胞增殖的抑制作用。方法　运用全细胞膜片钳技术 ,记录和分析 4 AP对SCLC中电压激活性K+ 电流的抑制作用 ;运用流式细胞仪 ,检测 4 AP对SCLC细胞增殖周期的影响 ;通过细胞体外增殖试验 ,证实 4 AP对SCLC细胞增殖的抑制作用。结果　 5mmol/L的 4 AP可将峰值外向K+ 电流 (除极化到 +80mV时激活 )从 1.2 2± 0 .11nA降低到 0 .5 9± 0 .10nA。流式细胞仪检测结果显示 ,应用 4 AP 3d后 ,能使SCLC细胞增殖周期中的G0 /G1期阻滞 ,S期和G1/M期的比率下降 (P <0 .0 1) ;0 .1,5 ,10 ,15 ,2 0mmol/L的 4 AP均能抑制SCLC细胞体外增殖 ,抑制的程度与药物的浓度、作用时间有关。结论　电压激活性K+ 通道在SCLC细胞增殖过程中起重要作用 ,K+ 通道阻滞剂能抑制SCLC细胞的增殖。更多还原

【Abstract】 Objective To study the inhibition of voltage-activated K + conductance and cell proliferation by 4-aminopyridine(4-AP) in the human small-cell lung cancer (SCLC). Methods Inhibition of voltage-activated K + current by 4-AP through the whole-cell patch-clamp technique in SCLC cell line was studied. The influence on the cell-cycle by 4-AP was observed by flow cytometry to identify the in vitro inhibition by 4-AP to the cell proliferation of the SCLC cell line. Results Exposure of the tumor cells to 5 mmol/L 4-AP reduced the peak outward K + current (evoked by a depolarization to +80 mV) from 1.22±0.11 nA( n =30) to 0.59±0.10 nA ( n =28). Flow cytometry results showed that cell population accumulated in the G 0/G 1 phase and a significantly reduced proportion in the S phase and G 1/G 2 phase cells after having been exposed to 4-AP for three days. Incubation of the SCLC cells with 0.1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-and time-dependent reduction in the number of viable cells as compared with the control. Conclusion The voltage-activated K + channels expressed by SCLC play an important role in SCLC cell proliferation. The proliferation of the SCLC cells is inhibited by K + channel antagonists.更多还原