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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 reduce the side effects of reversal agents and improve the reversal effect of drug resistance. METHODS: Homoharringtonin (HHT) was either alone or in combination with verapamil (VER) and tamoxifen (TAM), and drug susceptibility tests were performed using semi-solid agar colony culture. RESULTS: Both VER and TAM, alone or in combination, did not enhance the killing of K562-sensitive cells by HHT. However, both VER or TAM with no cytotoxic dose of 4μmol / L and 8μmol / L in KHT-resistant cell line K562 / H20 Obviously reversed the resistance to HHT in K562 / H20 cells, the IC50 decreased from 446.8 ± 0.08μg / L to 45.1 ± 0.02,22.4 ± 0.03 or 85.1 ± 0.03 respectively, 26.4 ± 0.02 μg / L. IC50 of drug-resistant cells was reduced to 30.4 ± 0.02 and 4.3 ± 0.04 μg / L, respectively, using a combination of 2 μmol / LVER and 4 and 8 μmol / LTAM clinically attainable plasma concentrations, with IC50 values of Sensitive strains are similar. HHT resistance was reversed at a constant concentration ratio of VER to TAM (1: 4) with a combined index value of <1, indicating a significant synergistic effect. Conclusion: VER or TAM alone can only partially reverse the drug resistance, the combination of the two have a clear synergistic effect.