[In vitro reversal of homoharringtonine resistance by the combination of tamoxifen and verapamil].
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.


CONCLUSIONS
HHT-resistance could be reversed by VER or TAM alone, and the combination of the two drugs showed a synergistic effect.
Han
J
J
Institute of Hematology, Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020.
Yan
W
W
Qian
Q
Q
Han
M
M
Qiu
L
L
Shi
H
H
Li
C
C
Li
X
X
Qi
J
J
Feng
S
S
D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D013629:Tamoxifen / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D006248:Harringtonines; D013629:Tamoxifen; D000077863:Homoharringtonine; D014700:Verapamil