联合应用化疗药物对三氧化二砷耐药白血病细胞的毒性实验研究

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (9): 1033-1037.

联合应用化疗药物对三氧化二砷耐药白血病细胞的毒性实验研究

卓家才¹, 汪明春^1,2, 陶小梅², 李明², 游伟文¹, 蔡力生¹, 刘焕勋¹

¹深圳市第二人民医院血液科, 深圳 518035, 广东;
²深圳市血液病研究所, 深圳 518035, 广东

收稿日期:2005-07-08 修回日期:2005-08-10 发布日期:2020-11-22
通讯作者: 卓家才,男,医学博士,主任医师,硕士生导师,研究方向:白血病的诊断和治疗。Tel:0755-83366388-8199 E-mail:jiacai8199@163.com

In vitro study on cytotoxicity of combination of some chemotherapy reagents towards arsenic trioxide-resistant leukemic cells

ZHUO Jia-cai¹, WANG Ming-chun^1,2, TAO Xiao-mei², LIMing², YOU Wei-wen¹, CAI Li-sheng¹, LIU Huan-xun¹

¹Department of Hematology, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China;
²Shenzhen Institute of Hematology, Shenzhen 518035, Guangdong, China

Received:2005-07-08 Revised:2005-08-10 Published:2020-11-22

摘要/Abstract

摘要： 目的: 探讨化疗药物联合应用对三氧化二砷(As2O3)耐药白血病细胞(K562/AS2)的毒性作用。方法: 细胞毒实验采用MTT 法, 二药合用时细胞毒性作用采用Chou-Talalay 联合指数法分析, 细胞表面P-糖蛋白(P-gp)和细胞内柔红霉素(DNR)浓度测定采用流式细胞术测定。结果: K562/AS2 细胞对三氧化二砷、柔红霉素、鬼臼乙叉苷(VP16)、三尖杉酯碱(H)、米托蒽醌(NVT)和阿糖胞苷(Ara-C)的耐药倍数分别为7.4、2.9、3.8、3.6、2.8 和1.1。K562 细胞和K562/AS2 细胞的细胞表面P-gp 或细胞内任意荧光强度无显著的统计学意义(P >0.05)。As2O3 与DNR、VP16、H 或NVT 联合应用时, 对K562、K562/AS2 和P-gp 表达的白血病细胞(K562/A02)细胞的联合指数均大于1。异搏定与DNR 联合应用时, 对K562 和K562/AS2 细胞的联合指数均大于1, 但是对K562/A02 细胞的联合指数均小于1。结论: K562/AS2 细胞对As2O3、DNR、VP16 和NVT 耐药, 其机制与P-gp 表达无关。异搏定联合应用DNR 可以逆转K562/A02 对DNR 的耐药性, 不能逆转DNR 对As2O3耐药细胞的耐药性。As2O3 与DN、VP16、H 和NVT联合应用时, 对K562、K562/AS2 和K562/A02 细胞的毒性均为拮抗作用。

关键词: 多药耐药, K562 细胞, 三氧化二砷, 柔红霉素, 足叶乙苷, 三尖杉酯碱, 米托蒽醌, 阿糖胞苷, 药物相互作用

Abstract: AIM: To explore the cytotoxicity of combination of some chemotherapy reagents towards K562/AS2, an arsenic trioxide (As2O3)-resistant leukemic cell line.METHODS: MTT assay was used to detect the cytotoxicity, and the combined drug effect of two drugs was analyzed with Chou-Talalay Combination Index (CI). Flow Cytometry was used to detect the P-glycoprotein on the cell surface and the introcellular concentration of daunorubicin (DNR).RESULTS: The relative resistant folds of K562/AS2 cell line to As2O3, DNR, VP16, harringtonine (H), NVT and Ara-cwere 7.4, 2.9, 3.8 and 1.1, respectively.The fluorescence of the P-glycoprotein on the surface or of the DNR inside the cells detected was not significantly different between the K562 and the K562/A02 cell line (P >0.05).The combination indexes of As2O3 combined with DNR, VP16, H or NVT to K562, K562/AS2 and K562/A02 cell lines were all above 1.The combination indexes of Verapamil combined with DNR to both K562 and K562/AS2 cell lines were above 1, and to the K562/A02 were below 1.CONCLUSION: K562/AS2 cell line is resistant to As2O3, DNR, VP16 and NVT.The mechanism of the drug resistance is not associated with the expression of P-gp.Verapamil combined with DNR can reverse the resistance of Pgp expressing leukemia cell, K562/A02, to DNR, but can not reverse the resistance of K562/AS2 cell line.The cytotoxicity of As2O3 combined with DNR, VP16, H and NVT shows antagonism to K562, K562/AS2 and K562/A02 cell lines.

Key words: multidrug resistance, k562 cell line, arsenic trioxide, daunorubicin, etoposide, harringtonine, mitoxantrone, cytarabine, drug interactions

中图分类号:

R979.1

卓家才, 汪明春, 陶小梅, 李明, 游伟文, 蔡力生, 刘焕勋. 联合应用化疗药物对三氧化二砷耐药白血病细胞的毒性实验研究[J]. 中国临床药理学与治疗学, 2005, 10(9): 1033-1037.

ZHUO Jia-cai, WANG Ming-chun, TAO Xiao-mei, LIMing, YOU Wei-wen, CAI Li-sheng, LIU Huan-xun. In vitro study on cytotoxicity of combination of some chemotherapy reagents towards arsenic trioxide-resistant leukemic cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 1033-1037.

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