硒联合5-FU对MCF-7乳腺癌细胞株和裸鼠移植瘤抑制作用研究  

Effect of Selenium combined with fluorouracil on breast carcinoma MCF-7 cell and its xenograft in nude mice

作　　者：张玉英[1] 谭亮[2] 伍思琪[1] 李艳萍[1] 

机构地区：[1]广东药学院人体解剖与组织胚胎学系,广东广州510006 [2]韶关学院医学院人体解剖与组织胚胎学系,广东韶关512026

出　　处：《中华肿瘤防治杂志》2014年第24期1952-1957,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：广东省科技计划(2012B031800311)

摘　　要：目的研究硒和5-氟尿嘧啶(5-FU)对MCF-7乳腺癌细胞株及其裸鼠移植瘤的抑制作用。方法实验分对照组(NS)、5-FU组、亚硒酸钠组(Na2SeO3)和联合用药组(5-FU+Na2SeO3)4组,体外培养MCF-7乳腺癌细胞,应用四甲基偶氮唑蓝(MTT)比色法检测各组MCF-7细胞的增殖情况,AnnexinⅤ-FITC/PI双染流式细胞技术检测各组细胞的凋亡率;建立裸鼠皮下移植瘤模型,监测各组裸鼠移植瘤的生长情况,免疫组织化学及蛋白质印迹法检测移植瘤组织中Bcl-2、Bax和Caspase-3蛋白表达情况。结果加药处理后,与对照组相比,各用药组MCF-7细胞的增殖均受到抑制,P值均<0.001,两药联合没有交互性,P=0.864;各用药组MCF-7细胞的凋亡明显增加,P值均<0.001,两药联合有交互作用,P=0.031;各用药组裸鼠移植瘤质量及体积均显著减小,P值均<0.001,两药联合有协同作用,P<0.001;免疫组织化学检测移植瘤组织中Bcl-2蛋白的表达,5-FU组(P=0.036)和Na2SeO3组(P=0.006)显著减少,两药联合没有交互性,P=0.957;Bax蛋白的表达,5-FU组(P=0.006)和Na2SeO3组(P=0.008)显著增加,两药联合没有交互性,P=0.516;Caspase-3蛋白的表达,5-FU组(P=0.004)和Na2SeO3组(P=0.002)显著增加,两药联合没有交互性,P=0.372;蛋白质印迹检测移植瘤组织中Bcl-2蛋白的表达,5-FU组和Na2SeO3组显著减少,P值均<0.001,两药联合有交互性,P<0.001;Bax蛋白表达,5-FU组和Na2SeO3组显著增加,P值均<0.001,两药联合有交互性,P=0.015;Caspase-3蛋白表达,5-FU组和Na2SeO3组显著增加,P值均<0.001,两药联合无交互性,P=0.139。结论硒和5-FU均可抑制MCF-7乳腺癌细胞株及其裸鼠移植瘤的生长,两药联合具体作用有待进一步实验证实。OBJECTIVE To study the effect of Selenium combined with fluorouracil on breast carcinoma MCF-7 cell and its xenograft in nude mice. METHODS Human breast carcinoma MCF-7 cells were cultured in vitro. The effects of Selenium and fluorouracil on proliferation and apoptosis of MCF-7 cells were detected by monotetrazolium（MTT） assay and flow cytometry （FCM）. The model of xenotransplanted breast carcinoma was established in nude mice using the MCF-7 cell line. Thirty two mice were randomized into 4 groups：saline （control） group, 5-FU group, Na2 SeO3 group, 5- FU＋ Na2SeO3 group. The weight and the volume of xenografts were measured to calculate the tumor inhibition rate. The expressions of Bcl-2,Bax and Caspase-3 protein in xenograft were detected by immunohistostaining and western blotting. RESULTS The proliferation of MCF-7 cells＇were suppressed after treated by Selenium and （or） fluorouracil （P〈 0. 001）. There was no interaction in combined use of Selenium and fluorouraeil （P=0. 864）; The apoptosis rates of MCF-7 ceils were increased in the experiment groups （P〈0. 001）. There was a cooperative interaction in the combination of two drugs （P=0. 031） ; The tumor weight and volume of the nude mice in the experiment groups were lower in comparison with those in the control group （P（0. 001）. There was a cooperative interaction in the combination of two drugs （P〈0. 001）; The expressions of Bcl-2 protein were decreased in 5-FU group （P= 0. 036） and Na2SeO3 group （P= 0. 006）, in comparison with those in the control group by immunohistostaining. There was no interaction in two drug combination （P=0. 957） ; The expressions of Bax protein were improved in 5 FU group （P：0. 006） and Na2SeO3 group （P=0. 008）, in comparison with those in the control group by immunohistostaining. There was no interaction in two drug combination （P=0. 516）~ The expressions of Caspase 3 protein were improved in 5-FU group （P= 0. 004） and Na2 SeO3 group （P= 0. 002）,

关 键 词：硒 亚硒酸钠 5-氟尿嘧啶 乳腺肿瘤 裸鼠 移植瘤 

分 类 号：R737.9[医药卫生—肿瘤]