【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。更多还原

【Abstract】 OBJECTIVE To study the effect of Selenium combined with fluorouracil on breast carcinoma MCF-7cell and its xenograft in nude mice.METHODS Human breast carcinoma MCF-7cells were cultured in vitro.The effects of Selenium and fluorouracil on proliferation and apoptosis of MCF-7cells were detected by monotetrazolium(MTT)assay and flow cytometry(FCM).The model of xenotransplanted breast carcinoma was established in nude mice using the MCF-7cell line.Thirty-two mice were randomized into 4groups:saline(control)group,5-FU group,Na2SeO3 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-3protein in xenograft were detected by immunohistostaining and western blotting.RESULTS The proliferation of MCF-7cells were suppressed after treated by Selenium and(or)fluorouracil(P<0.001).There was no interaction in combined use of Selenium and fluorouracil(P=0.864);The apoptosis rates of MCF-7cells 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-2protein 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 Na2SeO3group(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-3protein were improved in 5-FU group(P=0.004)and Na2SeO3group(P=0.002),in comparison with those in the control group by immunohistostaining.There was no interaction in two drug combination(P=0.372);The expressions of Bcl-2protein were decreased in the experiment groups in comparison with those in the control group by Western blotting(P<0.001).There was a cooperative interaction in two drug combination(P<0.001);The expressions of Bax protein were improved in the experiment groups in comparison with those in the control group by Western blotting(P<0.001).There was a cooperative interaction in two drug combination(P=0.015);The expressions of Caspase-3protein were improved in the experiment groups in comparison with those in the control group by Western blotting(P<0.001).There was no interaction in two drug combination(P=0.139).CONCLUSIONS Both Selenium and fluorouracil could inhibit the growth and promote apoptosis of MCF-7cells and its xenograft in nude mice.The cooperative effects in combined use of Selenium and fluorouracil were unconfirmed.更多还原