| 葡萄糖神经酰胺合成酶抑制剂PDMP对K562/A02细胞柔红霉素耐药逆转的研究 |
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| 引用本文： | 殷莉,陈宝安,程坚,丁家华,高冲,孙耘玉,王骏,赵刚,高峰,宋慧慧,鲍文,吴玮玮,王飞,梁艺琼,夏国华,王雪梅.葡萄糖神经酰胺合成酶抑制剂PDMP对K562/A02细胞柔红霉素耐药逆转的研究[J].中国实验血液学杂志,2010,18(1):79-84. |
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| 作者姓名： | 殷莉 陈宝安 程坚 丁家华 高冲 孙耘玉 王骏 赵刚 高峰 宋慧慧 鲍文 吴玮玮 王飞 梁艺琼 夏国华 王雪梅 |
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| 作者单位： | 1. 东南大学临床医学院附属中大医院血液科,江苏南京,210009
2. 东南大学生物电子学国家重点实验室,江苏南京,210096 |
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| 基金项目： | 国家自然科学基金(编号39970832,编号30740062); 高等学校博士学科点专项科研基金(编号20070286042) |
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| 摘 要： | 本研究旨在探讨葡萄糖神经酰胺合成酶(glucosylceramide synthase,GCS)抑制剂D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol(PDMP)hydrochloride对K562/A02细胞株柔红霉素(daunorubicin,DNR)耐药的逆转作用及其逆转机制。采用四甲基偶氮唑蓝(MTT)法检测不同浓度PDMP对K562细胞和K562/A02细胞的增殖抑制效应及其对K562/A02细胞DNR耐药逆转作用;用流式细胞术检测PDMP对K562/A02细胞内DNR浓度及细胞凋亡率的影响;半定量RT-PCR和Western blot方法检测K562及K562/A02细胞mdr1、GCS基因的表达以及PDMP对K562/A02细胞两种基因表达的影响。结果表明:DNR对K562和K562/A02细胞的IC50分别为0.23±0.02和7.15±0.24μg/ml,当PDMP≤20μmol/L时,对K562及K562/A02细胞株无明显生长抑制作用;20μmol/L和10μmol/L PDMP均能增加K562/A02细胞对DNR的敏感性,其耐药逆转倍数分别为2.59和1.69;两种浓度PDMP作用于耐药株48小时后能增加细胞内DNR浓度(p0.05)和细胞凋亡率(p0.01)。20μmol/L PDMP处理K562/A02细胞48小时后可在mRNA和蛋白水平下调GCS和mdr1基因的表达(p0.01)。结论:PDMP可以增强K562/A02细胞对DNR的敏感性,其机制可能与增加细胞内药物浓度及细胞凋亡率、下调GCS和mdr1基因表达有关。
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| 关 键 词： | 葡萄糖神经酰胺合成酶抑制剂 PDMP K562／A02细胞 多药耐药 |
Effect of PDMP, a Glucosylceramide Synthase Inhibitor, on Reversion of Daunorubicin Resistance in Human Leukemia Cell Line K562/A02 |
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| YIN Li,CHEN Bao-An,CHENG Jian,DING Jia-Hua,GAO Chong,SUN Yun-Yu,WANG Jun,ZHAO Gang,GAO Feng,SONG Hui-Hui,BAO Wen,WU Wei-Wei,WANG Fei,LIANG Yi-Qiong,XIA Guo-Hua,WANG Xue-Mei.Effect of PDMP, a Glucosylceramide Synthase Inhibitor, on Reversion of Daunorubicin Resistance in Human Leukemia Cell Line K562/A02[J].Journal of Experimental Hematology,2010,18(1):79-84. |
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| Authors: | YIN Li CHEN Bao-An CHENG Jian DING Jia-Hua GAO Chong SUN Yun-Yu WANG Jun ZHAO Gang GAO Feng SONG Hui-Hui BAO Wen WU Wei-Wei WANG Fei LIANG Yi-Qiong XIA Guo-Hua WANG Xue-Mei |
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| Institution: | ( Department of Hematology, The Affiliated Zhongda Hospital, Southeast University Clinical Medical College, Nanjing 210009, Jiangsu Province, China; 1National Key Laboratory of Bioelectronics ( Chien-Shiung Wu Laboratory) Southeast University, Nanjing 210096, Jiangsu Province, China) |
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| Abstract: | This study was purposed to investigate the reversal effect of glucosylceramide synthase(GCS) inhibitor D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol(PDMP) hydrochloride,on multidrug resistance in K562/A02 cells and its mechanism.The IC50(the half maximal inhibitory concentration) of PDMP was measured by MTT method.Cell apoptosis and intracellular daunoribicin(DNR) concentration were detected by flow cytometry.The expression of GCS and mdr1 genes were assayed by semi-quantitative reverse transcr... |
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| Keywords: | glucosylceramide synthase inhibitor PDMP K562/A02 cell multidrug resistance |
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