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PHI逆转K562/A02细胞阿霉素耐药的机制

Mechanism of phenylhexyl isothiocyanate reversing multidrug resistance to adriamycin in K562/A02 cell line

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【作者】 陈宝安袁鹏夏国华程坚马旭东刘德龙鹿全意

【Author】 CHEN Baoan,YUAN Peng,XIA Guohua,et al.Department of Hematology,Affiliated Zhongda Hospital,Southeast University,Nanjing 210009,CHINA

【机构】 东南大学附属中大医院血液病科福建省漳州市医院Department of Medicine,New York Medical College厦门大学附属中山医院

【摘要】 目的探讨异硫氰酸苯乙酯(PHI)逆转K562/A02细胞株阿霉素(ADM)耐药的可能机制。方法将耐ADM的人慢性粒细胞白血病K562/A02细胞株分别与不同浓度(0,5,10,20,30,40和50μM)的PHI共同孵育后,流式细胞术检测细胞周期、细胞内ADM浓度以及P-糖蛋白1(P-gp1)表达水平;逆转录聚合酶链反应(RT-PCR)检测PHI作用前后细胞内mdrl mRNA的转录水平。结果与对照组相比,联合作用48h后,随着PHI浓度的增加G2期细胞逐渐减少,G1期细胞明显增多,而S期细胞无明显变化;K562/A02细胞内ADM平均荧光强度均高于对照组;K562/A02细胞mdrl mRNA表达下降和P-gp1表达下调(P<0.05)。结论 PHI逆转K562/A02细胞耐药机制可能与细胞G1期阻滞和P-gp1表达下调有关。

【Abstract】 Objective To elucidate the mechanism of phenylhexyl isothiocyanate (PHI) on the reversal of K562/A02 cell line.Methods After adriamycin(ADM) resistant K562/A02 cells were incubated with different concentrations of PHI(5,10,20,30,40 and 50 μM) or without PHI (control),flow cytometry(FCM)was used to evaluate cell cycle distributions,intracellular concentration of ADM,and the expression of P-gp1,respectively.Furthermore,mdrl mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR) assay before and after use of PHI.Results The number of K562/A02 cells of G2 phase decreased and G1 phase increased,while the S phase had no obvious changes.The intracellular concentrations of ADM in K562/A02 cells were all higher than those in control groups.The transcription of mdrl mRNA and expression of P-gp1 were decreased and down-regulated with the increase of PHI,respectively (P<0.05) when compared to those of control groups.Conclusion Multidrug resistance of K562/A02 can be partly reversed by PHI,which may be related to the arrest of G1 and the decrease of P-gp1 expression.

【基金】 国家自然科学基金(39970832,30740062)
  • 【文献出处】 江苏医药 ,Jiangsu Medical Journal , 编辑部邮箱 ,2010年10期
  • 【分类号】R733.7
  • 【下载频次】92
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