拓扑异构酶Ⅱ抑制剂诱导SUNE-1鼻咽癌细胞凋亡的研究  

Apoptosis of Nasopharyngeal Carcinoma Cells Induced by inhibitors of Topoisomerase Ⅱ,ADM and THP

作　　者：向燕群[1] 姚和瑞[2] 郭翔[1] 洪明晃[1] 曹素梅[1] 闵华庆[1] 

机构地区：[1]中山大学肿瘤防治中心鼻咽癌科,广州市510060 [2]中山大学附属第二医院肿瘤科

出　　处：《中国肿瘤临床》2005年第24期1406-1409,共4页Chinese Journal of Clinical Oncology

基　　金：广东省社会发展领域科技计划项目资助(编号:粤科社[2003]245号)

摘　　要：目的:探讨拓扑异构酶Ⅱ(TopoⅡ)抑制剂吡喃阿霉素(THP)、阿霉素(ADM)诱导鼻咽低分化鳞癌细胞株SUNE-1细胞凋亡的作用;并检测药物作用后SUNE-1线粒体膜电位及Livin表达水平的变化。方法:采用MTT法检测THP、ADM对SUNE-1细胞的生长抑制,Annenxin V FITC染色检测凋亡早期细胞,流式细胞仪检测线粒体膜电位改变和Livin的表达情况。结果:ADM和THP对SUNE-1具有较强的体外抗肿瘤作用,随着药物浓度增高细胞增殖抑制率增高,其IC50分别为0.004 1±0.000 3"g/ml和0.003 8±0.000 8"g/ml(P=0.542)。随着药物作用时间的增加,SUNE-1细胞凋亡率逐渐增高,同时伴有线粒体内膜电负性逐渐增加。ADM、THP诱导SUNE-1细胞凋亡中出现Livin的表达上调,但THP作用后表达上调的程度较ADM低。结论:TopoⅡ抑制剂蒽环类药物THP、ADM具有抑制细胞增殖和诱导鼻咽低分化鳞癌细胞株SUNE-1细胞凋亡的作用。TopoⅡ抑制剂作用鼻咽癌细胞后诱导IAP蛋白中的Livin表达上调,但THP作用后所引起的Livin表达上调不如ADM显著,因此THP在治疗鼻咽癌时可能具有更好的应用价值,需在临床中进一步证实。Objective： To evaluate the cytotoxieities of inhibitors of Topo Ⅱ including adriamycin and pirarubicin to low differentiated squamouse nasopharyngeal carcinoma （NPC） cell line SUNE-1 and the apoptotic effect inducing and the expression of Livin when treated with these drugs. Methods： The cytotoxicities of adriamycin and pirarubicin to SUNE-1 were detected by MTF assay. The cell-apoptosis rate was analyzed by Annenxin V FITC staining and detected using flow cytometry. The changes of mitochondrial transmembrane potential and expression of Livin were detected using flow cytometry. Results： The proliferation of SUNE-1 could be inhibited by adriamycin and pirarubicin. The effects were dose-dependent. The IC50 of adriamycin and pirarubicin to SUNE-1 was 0.0041±0.0003 ug/ml and 0.0038±0.0008ug/ml, respectively （P=0.542）. The apoptosis rate and negative mitochondrial trans- membrane potential increased with the treatment time. SUNE-1 presented change of Livin expression when treated with ADM or THP, but the increased level of Livin expression induced by THP was lower than those induced by ADM. Conclusion： Adriamycin and pirarubicin can inhibit the proliferation and induce apoptosis of SUNE-1 in vitro. They can upregulate expression of Livin in NPC cells. But there is a relatively lower level in expression of Livin when treated with pirarubicin than treated with adriamyein. This suggests that pirarubinein maybe more effeetive to treat NPC patients than adriamyein which need further confirmation in clinical praetiee.

关 键 词：鼻咽癌 LIVIN 细胞凋亡 线粒体膜电位 

分 类 号：R739.63[医药卫生—肿瘤]