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作 者:蔡晓辉[1,2] 陈宝安[1,2] 程坚[1,2] 王筠[1,2] 丁家华[1,2] 鲍文[1,2] 仲悦娇[1,2] 高峰[1,2] 许文林[3] 沈慧玲[3] 魏虎来[4] 陈静[4]
机构地区:[1]东南大学医学院 [2]东南大学附属中大医院血液科,江苏南京210009 [3]江苏大学附属人民医院血液科,江苏镇江212002 [4]兰州医学院血液病研究所,甘肃兰州730000
出 处:《中国实验血液学杂志》2011年第1期24-27,共4页Journal of Experimental Hematology
基 金:国家863计划重点项目(编号2007AA0222006);国家自然科学基金资助项目(编号39970832;编号30740062);高等学校博士专用科学基金项目(编号20070286024)
摘 要:本研究探讨5-溴汉防己甲素(BrTet)联合柔红霉素(DNR)治疗耐药慢性髓系白血病的潜在可能性及其相关机制。采用流式细胞术检测DNR,BrTet或DNR和BrTet联合作用K562/A02细胞48小时后凋亡率情况;采用RT-PCR法检测对照组K562细胞、耐药K562/A02细胞及DNR或(和)BrTet作用于K562/A02细胞48小时后存活蛋白(survivin)mRNA表达水平;采用Western blot法检测各组细胞survivin蛋白表达水平。结果表明:BrTet与DNR联合作用对K562/A02细胞的诱导凋亡率较其余各组显著升高,同时联合用药组K562/A02细胞survivin mRNA和蛋白的表达较空白对照组和单药组下调,K562/A02细胞survivin表达较K562细胞升高。结论:BrTet联合DNR能有效逆转耐药,促进K562/A02细胞凋亡,其机制可能与survivin表达下调有关。The aim of this study was to investigate the potential benefit of combination therapy with 5-bromotetrandrine(5-BrTet) and daunorubicin(DNR) on chronic leukemia.The apoptosis of K562/A02 cells treated by DNA,BrTet and BrTet combined with DNR for 48 hours was detected by flow cytometry;the expressions levels of survivin mRNA and protein K562/A02 cells treated by DNR,BrTet and BrTet combined with DNR and in untreated K562 cells for 48 hours were measured by RT-PCR and Western blot respectively.The results showed that the combination of BrTet with DNR increased apoptotic rate of K562/A02,down-regulated the expression levels of survivin mRNA and protein in K562/A02 cells as compared with blank control and cells treated by BrTet or DNR alone,the survivin expression in K562/A02 cells was higher than that in K562 cells.It is concluded that the combination of BrTet with DNR can effectively reverse the multidrug resistance of K562/A02 cells,promote the apoptosis of K562/A02 cells,the mechanism of which may be related with down-regulation of survivin expression.Survivin may be a target for the treatment of MDR in hematopoietic malignancies.
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