5-溴粉防己碱与粉防己碱对K562/A02细胞多药耐药性逆转作用的比较

王珏琼; 陈宝安; 程坚; 许文林; 孙新臣

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5-溴粉防己碱与粉防己碱对K562/A02细胞多药耐药性逆转作用的比较

首发时间：2008-01-30

王珏琼 ¹ 陈宝安 ¹ 程坚 ¹ 许文林 ² 孙新臣 ³

1、东南大学临床医学院，东南大学中大医院血液科
2、江苏大学附属人民医院血液科
3、东南大学中大医院肿瘤科

摘要：5-溴粉防己碱（5-bromotetrandrine, BrTet）是中草药提取的双苄基异喹啉生物碱——粉防己碱（汉防己甲素，Tetrandrine, Tet）的溴化产物，具有逆转P-糖蛋白(P-glyeoprotein，P-gp)介导的肿瘤多药耐药(muhidrug resistance，MDR)作用。本研究旨在比较5-溴粉防己碱与传统粉防己碱对人白血病细胞K562/A02多药耐药的逆转作用，为BrTet作为耐药逆转剂的临床应用提供理论依据。方法：采用甲基四唑蓝法（MTT）法检测不同浓度BrTet对K562细胞和K562/A02细胞的增殖抑制效应；MTT法检测阿霉素(adfiamycin，ADM) K562、K562/A02细胞增殖的抑制作用及加用BrTet、Tet时的变化，计算半数抑制量（50% Inhibiting Concentration, IC50）及逆转倍数（Fold Reversal, FR）；流式细胞仪（Flow Cytometry, FCM）法检测K562细胞、K562/A02细胞膜表面P-gp的表达以及各组细胞内ADM蓄积变化。结果：K562/A02对ADM的耐药倍数为49.51倍。1.0 µmol/L及更低浓度的BrTet对K562和K562/A02细胞无明显细胞毒性作用。加入1.0 µmol/L的Tet后，K562/A02细胞对ADM的耐药倍数为12.17倍。加入0.25 µmol/L、0.5 µmol/L和1.0 µmol/L的BrTet后，K562/A02细胞对ADM的耐药倍数分别为17.88、9.9 和4.24倍。1.0 µmol/L的BrTet可明显提高ADM在K562/A02细胞内的蓄积，降低细胞膜表面P-gp的表达。与Tet作用相比，差异具有显著性。结论：BrTet及Tet均可逆转耐药，且前者较后者逆转作用更强，其逆转效果与药物浓度有关，逆转机制与抑制P-gp的表达、增加细胞内抗肿瘤药物浓度有关。

关键词：多药耐药逆转剂 5-溴粉防己碱粉防己碱 K562/A02

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Reversal of P-Glycoprotein-Dependent Resistance to Adriamycin by 5-bromotetrandrine in K562/A02 Cell Line in vitro

WANG Jue-Qiong ¹ CHEN Bao-An ¹ CHENG Jian ¹ XU Wen-Lin ² SUN Xin-Chen ³

1、Department of Hematology, Zhongda Hospital, Clinical Medical College, Southeast University
2、Department of Hematology, People’s Hospital, Jiangsu University
3、Department of Oncology, Zhongda Hospita

Abstract：BACKGROUND & OBJECTIVE: Bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), could effectively reverse P-glycoprotein mediated multidrug resistance. The present study was to investigate the reversal effect of BrTet on multidrug resistance of human leukemia cell line K562/A02 in vitro and compare it with that of Tet. METHODS: The effects of BrTet on the proliferation of K562 and K562/A02 cells were observed by MTT assay. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The effects of BrTet or Tet on ADM accumulation and the protein levels of P-glycoprotein (P-gp) were analyzed by flow cytometry(FCM), respectively. RESULTS: BrTet at the concentration of 1.0 µmol/L showed no significant cytotoxicity to K562 and K562/A02 cells. The resistance of K562/A02 cells to ADM was 49.51 foIds of that Of K562 cells. When added 1.0 µmol/L Tet the chemosensitivity of K562/A02 cells to ADM was increased to 12.17 folds；when added 0.25 µmol/L, 0.5 µmol/L and 1.0 µmol/L BrTet，the chemosensitivity was increased to 17.88, 9.9 and 4.24 folds, respectively. Flow cytometry assay showed that 1.0 µmol/L BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells and its potency was greater than that of Tet at the same concentrations. BrTet also inhibited the overexpression of P-gp in K562/A02 cells. CONCLUSIONS: BrTet showed significant MDR reversal activity in vitro. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs. BrTet may be a promising MDR modulator for eventual assessment in the clinic.

Keywords： K562/A02 cells Multidrug resistance Modulator Bromotetrandrine Tetrandrine

基金：

1. 国家自然科学基金资助项目,国家自然科学基金资助项目,江苏省科技厅社会发展项目（（No. 39970832）,（No. 3074006）,（No. BS2004024））

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王珏琼，陈宝安，程坚，等. 5-溴粉防己碱与粉防己碱对K562/A02细胞多药耐药性逆转作用的比较[EB/OL]. 北京：中国科技论文在线 [2008-01-30]. https://www.paper.edu.cn/releasepaper/content/200801-885.

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论文编号	200801-885
论文题目	5-溴粉防己碱与粉防己碱对K562/A02细胞多药耐药性逆转作用的比较
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