新型多胺缀合物NMMB逆转K562/ADM细胞多药耐药及其机制

J4 ›› 2010, Vol. 36 ›› Issue (2): 238-241.

新型多胺缀合物NMMB逆转K562/ADM细胞多药耐药及其机制

盖晓东,程鹏飞,历春,冯凯,王超杰

1.北华大学基础医学院病理学教研室,吉林吉林 132001；2.河南大学天然产物与药物化学研究所,河南大学天然产物与药物化学研究所,河南开封 475004

收稿日期:2009-09-22 出版日期:2010-03-28 发布日期:2010-03-28
通讯作者: 王超杰(Tel:0432-4608104,E-mail:wcjsxq@henu.edu.cn) E-mail:wcjsxq@henu.edu.cn
作者简介:盖晓东(1962-),女,吉林省吉林市人|教授,医学博士,主要从事肿瘤分子病理学研究。

Effect of a novel polyamine conjugate on MDR reversal of K562/ADM cells and its mechanism

GAI Xiao-Dong, CHENG Peng-Fei, LI Chun, FENG Kai, WANG Chao-Jie

1.Department of Pathology,School of Basic Medical Sciences,Beihua University,Jilin 132013,China;2.Institute of Natural Products and Medicinal Chemistry,Henan University,Kaifeng 475004,China

Received:2009-09-22 Online:2010-03-28 Published:2010-03-28
Supported by:
国家自然科学基金资助课题(20472016);吉林省科技厅自然科学基金资助课题(200505246)

摘要/Abstract

摘要：

目的：研究新型多胺缀合物NMMB对白血病细胞株K562/ADM的多药耐药（MDR）逆转作用，并进一步探讨其耐药逆转机制。方法：分别以不同浓度的NMMB(10～1 000 mg/L)作用于体外培养的K562和K562/ADM细胞24 h,采用MTT 法检测细胞增殖抑制率,确定NMMB的非毒性剂量;采用非毒性剂量,NMMB 0、 2.5 、5.0 和10.0 mg/L组，分别与不同浓度ADM（0.25～100.00 mg/L）联合作用，检测各组细胞生长抑制50%的ADM浓度，即IC50，计算逆转倍数；利用流式细胞术检测NMMB联合ADM作用后K562/ADM 细胞内ADM蓄积程度和细胞周期变化。结果：随着NMMB浓度的增加，细胞增殖抑制率也相应增加，呈剂量-效应关系；NMMB的最大无毒剂量为12.5 mg/L，逆转倍数为4倍；NMMB可明显提高ADM在K562/ADM细胞内的蓄积，与未加NMMB对照组比较差异有显著性（P<0.05）；K562/ADM细胞被阻滞在G0/G1期，与未加NMMB对照组比较差异有显著性（P<0.01）。结论：NMMB对白血病耐药细胞株K562/ADM有增殖抑制和多药耐药逆转作用，其部分逆转机制可能是通过增加细胞内化疗药物蓄积和将K562/ADM细胞阻滞在G0/G1期而实现的。

关键词: 多胺缀合物；多药耐药；耐药逆转；K562/ADM细胞

Abstract:

Abstract:Objective To investigate the reversal effect of a novel polyamine conjugate,NMMB,on multidrug resistance (MDR) of myelogenous leukemia K562/ADM cells and discuss the possible correlative mechanism.Methods K562 and K562/ADM cells in culture medium were treated with NMMB (10-1 000 mg/L) respectively.The inhibitory rates of these cells were measured by MTT assay.Non-cytotoxic dose of NMMB was determined. K562/ADM cells at logarithmic growth phase were randomly divided into ADM control,NMMB 2.5,5.0,10.0 mg/L groups.The inhibitory rate 50% (IC50) and the reversal index in all groups were determined.The effects of NMMB on ADM accumulation in K562/ADM cells and cell cycle were examined by flow cytometry (FCM).Results The inhibitory rates were significantly increased when the cells were treated with different doses of NMMB (10-1 000 mg/L) in a dose-dependent manner.The available reversal concentration of NMMB was 12.5 mg/Land the reversal index was 4 folds on K562/ADM cells.ADM accumulation in K562/ADM cells was significantly increased (P<0.05).The cells were blocked at the period of G0/G1 (P<0.01).Conclusion NMMB has an effect on proliferation inhibition and MDR reversal of K562/ADM cell line.The reversal mechanisms of NMMB may be due to increasing the accumulation of chemo-drugs in cells and arresting the cells at 0/G1 phase.

Key words: polyamines conjugate;multi-drug resistance;reversal of drug resistance;K562/ADM cell

中图分类号:

R733.7

盖晓东, 程鹏飞, 历春, 冯凯, 王超杰. 新型多胺缀合物NMMB逆转K562/ADM细胞多药耐药及其机制[J]. J4, 2010, 36(2): 238-241.

GAI Xiao-Dong, CHENG Peng-Fei, LI Chun, FENG Kai, WANG Chao-Jie. Effect of a novel polyamine conjugate on MDR reversal of K562/ADM cells and its mechanism[J]. J4, 2010, 36(2): 238-241.

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