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 byinhibitors of Topoisomerase Ⅱ, ADM and THP

  • 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 3μg/ml和0.003 8±0.000 8μg/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。

     

    Abstract: Objective: To evaluate the cytotoxicities of inhibitors of TopoⅡincluding adriamycinand pirarubicin to low differentiated squamouse nasopharyngeal carcinoma (NPC) cell line SUNE-1 andthe apoptotic effect inducing and the expression of Livin when treated with these drugs.Methods: Thecytotoxicities of adriamycin and pirarubicin to SUNE-1 were detected by MTT assay. The cell-apopto-sis rate was analyzed by Annenxin V FITC staining and detected using flow cytometry. The changes ofmitochondrial 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 effectswere dose-dependent. The IC 50 of adriamycin and pirarubicin to SUNE-1 was 0.0041±0.0003 μg/mland 0.0038±0.0008μg/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 expressionwhen treated with ADM or THP, but the increased level of Livin expression induced by THP was lowerthan those induced by ADM.Conclusions: Adriamycin and pirarubicin can inhibit the proliferation andinduce 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 adri-amycin. This suggests that pirarubincin maybe more effective to treat NPC patients than adriamycinwhich need further confirmation in clinical practice.

     

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