摘要
目的：降低逆转剂的毒副作用，提高耐药的逆转效果。方法：用异搏定（ＶＥＲ）和它莫西芬（ＴＡＭ）单独或联合体外逆转高三尖杉酯碱（ＨＨＴ）耐药，药敏试验采用半固体琼脂集落培养法。结果：ＶＥＲ和ＴＡＭ单独或联合均不能增强ＨＨＴ对Ｋ５６２敏感细胞的杀伤；而在ＨＨＴ耐药细胞株（Ｋ５６２／Ｈ２０）中，无细胞毒性剂量４μｍｏｌ／Ｌ和８μｍｏｌ／Ｌ的ＶＥＲ或ＴＡＭ均能明显逆转Ｋ５６２／Ｈ２０细胞对ＨＨＴ的耐药，ＩＣ５０由４４６．８±０．０８μｇ／Ｌ分别下降为４５．１±０．０２，２２．４±０．０３或８５．１±０．０３，２６．４±０．０２μｇ／Ｌ。采用临床可达到血药浓度的２μｍｏｌ／ＬＶＥＲ与４和８μｍｏｌ／ＬＴＡＭ联合，耐药细胞的ＩＣ５０分别降为３０．４±０．０２和４．３±０．０４μｇ／Ｌ，后者的ＩＣ５０与敏感株相近。以恒定浓度比ＶＥＲ与ＴＡＭ联合（１∶４）逆转ＨＨＴ耐药，联合指数值均＜１，有明显的协同作用。结论：单独使用ＶＥＲ或ＴＡＭ仅能部分逆转耐药，两者联合有明显的协同作用。
Objective:To investigate the reversal of homoharringtonine (HHT) resistance by tamoxifen (TAM) or verapamil(VER) alone or in combination. Methods:The drug sensitivity test was performed with semisolid agar culture.Results:The cytotoxicity of HHT to K562/S cells was not enhanced by TAM or VER alone or in combination,but HHT resistance in HHT resistant cells (K562/H20) was reversed by VER and TAM at nontoxic doses (4μmol/L or 8μmol/L).The IC 50 of K562/H20 for HHT decreased from 446.8±0.08μg/L to 45.1±0.02μg/L in the presence of 4μmol/L of VER , to 22.4±0 03μg/L in 8 μmol/L of VER,to 85.1±0.03μg/L in 4μmol/L of TAM and to 26.4±0.02μg/L in 8μmol/L of TAM.In the presence of combinations of 2μmol/L VER and 4μmol/L TAM and of 2μmol/L VER and 8μmol/L TAM,IC 50 of K562/H20 decreased to 30.4±0.02μg/L and 4.3±0.04μg/L, respectively.Conclusion: HHT resistance could be reversed by VER or TAM alone,and the combination of the two drugs showed a synergistic effect.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
1997年第3期143-146,共4页
Chinese Journal of Hematology
关键词
异搏定
它莫西芬
逆转
高三尖杉酯碱
耐药性
Verapamil Tamoxifen Homoharringtonine Drug resistant cell line Reversal of drug resistance
