钾通道阻滞剂对人肺腺癌细胞增殖和凋亡的影响  

Effect of potassium channel blocker on proliferation and apoptosis of human pulmonary adenocarcinoma cells

作　　者：李雪连[1] 乔国芬[1] 单宏丽[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药理学教研室黑龙江省生物医药工程重点实验室,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2006年第1期13-16,共4页Journal of Harbin Medical University

摘　　要：目的研究电压依赖性延迟整流钾通道阻断剂4-氨基吡啶(4-aminopyridine,4-AP)、钙离子激活钾通道阻断剂四乙铵(tetraethylammonia,TEA)对人肺腺癌细胞(AGZY-83-a)的影响,并探讨人肺腺癌细胞株凋亡的机制。方法体外细胞培养法培养人肺腺癌细胞株,采用MTT法检测不同浓度4-AP、TEA对细胞增殖的影响。透射电镜、流式细胞术(FCM)检测细胞凋亡情况。比色法检测细胞内Caspase-3活性改变。结果不同浓度的4-AP、TEA作用于细胞48h后,与对照组相比各组吸光度值(A490)均明显降低(n=10,P<0.001),并且呈浓度依赖关系。4-AP、TEA组的IC50为3.59mmol/L和3.97mmol/L。4-AP及高浓度的TEA使人肺腺癌细胞株细胞凋亡率增加。经4-AP、TEA处理48h的AGZY-83-a细胞内Caspase-3的A405较正常对照组有显著增加(n=6,P<0.001)。结论钾通道阻滞剂4-AP、TEA对AGZY-83-a细胞增殖有明显的抑制作用,抑制率与药物浓度正相关。诱导人AGZY-83-a细胞凋亡,4-AP和TEA诱导AGZY-83-a细胞凋亡的过程中细胞内Caspase-3活性增加。Objective To investigate the effect of voltage dependent K^＋ channel blocker （4-aminopyridine,4- AP） and calcium activated K^＋ channel blocker （tetraethylammonia, TEA）on human pulmonary adenocarcinoma AGZY-83-a cell line and to explore its mechanism. Methods The inhibitory rate of cultured AGZY-83-a cell treated with 4-AP, TEA at various concentration was observed with MTT assay. Apeptosis was detected with flow cytometry and electronic microscope. Cellular caspase-3 activities were observed with colorimetric method. Resuits 48h after AGZY-83-a cell treated with different concentration of 4-AP, TEA administration, the absorbancy （A490） was obviously lower than the control group accordingly（ n = 10, P 〈 0.001 ）, showing a concentration-dependent manner.The ICso of 4-AP, TEA on cells were 3.59mmol/L and 3.97mmol/L, respectively. The flow cytometry analysis showed that 4-AP and high concentration TEA increased the percentage of early phase apoptosis. The cellular caspase-3 A405 of AGZY-83-a ceil treated with 4-AP, TEA was obviously higher than control group （ n = 6, P 〈 0.001 ）. Conclusion The proliferation of AGZY-83-a cell is inhibited by potassium channel blocker 4-AP, TEA in concentration-dependent manner. 4-AP, TEA induce apeptosis of AGZY- 83-a cell. Caspase-3 is actived when 4-AP, TEA induce apeptosis of AGZY-83-a cell.

关 键 词：钾通道阻滞剂 4-氨基吡啶 四乙铵 AGZY-83-a 半胱氨酸酶3 

分 类 号：R734.2[医药卫生—肿瘤]