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 (4micromol/L or 8micromol/L). The IC50 of K562/H20 for HHT decreased from 446.8 +/- 0.08microg/L to 45.1 +/- 0.02microg/L in the presence of 4micromol/L of VER, to 22.4 +/- 0.03microg/L in 8micromol/L of VER, to 85.1 +/- 0.03microg/L in 4micromol/L of TAM and to 26.4 +/- 0.02microg/L in 8micromol/L of TAM. In the presence of combinations of 2micromol/L VER and 4micromol/L TAM and of 2micromol/L VER and 8micromol/L TAM, IC50 of K562/H20 decreased to 30.4 +/- 0.02microg/L and 4.3 +/- 0.04microg/L, respectively.
Conclusion: HHT-resistance could be reversed by VER or TAM alone, and the combination of the two drugs showed a synergistic effect.