川芎嗪联合三氧化二砷逆转K562/ADM细胞多药耐药的实验研究 |
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引用本文: | 王婷,双跃荣,庄小捷,罗秋莲. 川芎嗪联合三氧化二砷逆转K562/ADM细胞多药耐药的实验研究[J]. 实用癌症杂志, 2009, 24(2): 121-124,134 |
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作者姓名: | 王婷 双跃荣 庄小捷 罗秋莲 |
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作者单位: | 1. 南昌大学医学院,330006 2. 江西省肿瘤医院,330029 |
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摘 要: | 目的探讨川芎嗪与三氧化二砷联合逆转耐药人红白血病细胞株K562/ADM多药耐药的效果。方法采用WST-8法测定细胞的药敏性及抗药性逆转,应用流式细胞术检测细胞凋亡、细胞内ADM浓度、P-gp蛋白的表达,采用免疫细胞化学二步法检测细胞GST-π表达。结果非细胞毒性浓度的TMP(20μg/ml)及As2O3(0.5μmol/L)可降低ADM对K562/ADM细胞的IC50(P〈0.05),2种药物联合应用对ADM的逆转倍数明显高于两者单独应用(P〈0.05),而且也高于两者单独应用之和;两者以非细胞毒性浓度联合应用提高K562/ADM细胞内ADM浓度和细胞凋亡百分率,作用大于两药单独应用,并且明显下调细胞P-gp和GST-π表达(P〈0.05,P〈0.01)。结论非细胞毒性剂量的TMP和As2O3,均可部分逆转有多药耐药表型的细胞株K562/ADM对阿霉素的耐药性,两者联合应用效果优于单独应用,具有协同作用,其机制可能与下调P-gp和GST-π表达有关。
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关 键 词: | K562/ADM细胞株 多药耐药 川芎嗪 三氧化二砷 |
The Experimental Studies of Tetramethylpyrazine in Combination with Arsenic Trioxide on the Reversal of Multidrug Resistance in K562/ADM Cell Line |
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Affiliation: | WANG Ting, SHUANG Yue-rong, ZHUANG Xiao-jie, et al. (Medical College of Nanchang University, Nanchang, 330006) |
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Abstract: | Objective To evaluate the effect of tetramethylpyrazine in combination with arsenic trioxide on the reversal of muhidrug resistance in K562/ADM cell line. Methods The sensitivity of cell lines and the reversal of drug resistance were determined with WST - 8 method. The cell apoptosis and the concentration of intracellular ADM and P - gp expression were measured with flow cytometry(FCM) , and the expression of GST-πin cells was assessed by immunohistochemical methods. Results TMP(20 μg/ml)and As2 03 (0. 5 μmol/L)at the non -cytotoxic dose could markedly decrease the IC50 value of K562/ADM cell line to adriamycin(ADM) (P 〈 0.05 ). TMP combined with As203 at the non -cytotoxic dose strongly improved drug resistance reversal effect, which was larger than the single application of TMP or As2 03 respectively and their summation (P 〈 0.05 ). TMP combined with As2O3 at the non - cytotoxic dose strongly increase intracellular ADM concentration and apoptosis percentage of K562/ADM cell line, which was larger than the single application of TMP or As2O3 respectively. TMP combined with As2O3 at the non - cytotoxic dose down - regulate strongly both of P - gp and GST -πexpression ( P 〈0. 05, P 〈 0.01 ). Conclusion TMP and As2O3 al the non-cytotoxic dose could partly reverse the MDR of K562/ADM. The effect of combination of two agents were superior to that of single agent due to their synergism, which may be related to down - regulating of P - gp and GST - πexpression. |
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Keywords: | K562/ADM cell line Multidrug resistance(MDR) Tetramethylpyrazine(TMP) Arsenic trioxide( As2O3 ) |
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