摘要
目的:探讨磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)抑制剂LY294002(LY)和wortmannin(Wort)对米托蒽醌(mitoxantrone,MIT)耐药的人乳腺癌细胞株MCF-7/MIT耐药性的逆转作用。方法:LY或Wort与MIT联合作用耐药细胞株MCF-7/MIT后,在光学显微镜下记录细胞生长状况,MTT法检测细胞增殖和细胞活性。FCM法检测细胞内MIT的积聚。罗丹明123(rhodamine 123,Rh123)染色法检测细胞线粒体膜电位。碘化丙啶(propidium iodide,PI)染色法检测细胞周期。结果:LY和MIT联合作用可显著增强MIT引起的MCF-7/MIT细胞增殖抑制作用、由MIT引起的线粒体膜电位下降以及细胞周期S和G2/M期阻滞,其作用机制与LY增加MIT在MCF-7/MIT细胞内的积聚有关;Wort对MIT的药效无明显增强作用。结论:LY和MIT联合作用可显著提高耐药细胞株MCF-7/MIT对MIT的敏感度。
Objective ： To investigate the reversing effect of phosphatidylinositol 3-kinase （PI3K） inhibitors, LY294002 （LY） and wortmannin （Wort）, on the drug resistance of mitoxantrone （MIT）-resistant human breast cancer MCF-7/MIT ceils. Methods： Drug-resistant MCF-7/MIT ceils were treated with LY or Wort combined with MIT. Cell viability and proliferation were measured using the MTT assay and morphological changes were recorded by microscopy. Intracellular accumulation of MIT in MCF-7/MIT cells was detected by flow cytometry. Mitochondrial membrane potential was determined by rhodamine 123 staining. Cell cycle was examined by propidium iodide staining. Results：LY significantly enhanced the cytotoxicity of MIT to MCF-7/MIT cells. In LY and MIT cotreated cells, the percentage of ceils arrested at S and G/M phases and the mitochondrial membrane potential decreased significantly compared with single LY- or MIT-treated cells. The mechanism was related with increased accumulation of NIT in MCF-7/MIT cells induced by LY. While Wort, another PI3K inhibitor, did not significantly enhance the cytotoxie effects of MIT. Conclusion： The PI3K inhibitor significantly enhances the sensitivity of MCF-7/MIT cells to MIT.
出处
《肿瘤》
CAS
CSCD
北大核心
2009年第7期620-625,共6页
Tumor
基金
国家“八六三”计划资助项目(编号:2006AA020501)
上海市卫生局科研课题计划项目(编号:2006060)
作者简介
CHEN Fei（陈菲）E-mail：faithchen@yahoo.com
CHEN Ji-wu（陈季武）E-mail：jwchen@bio.ecnu.edu.cn
