OBJECTIVETo investigate the effect of phenylhexyl isothiocyanate (PHI) on the drug-resistance to imatinib in K562/G01 cell line and to elucidate its possible mechanisms.

METHODSMTT assay was employed to access K562/G01 cell growth inhibition after exposure to PHI and/or imatinib at different concentrations. Apoptotic rate of K562/G01 cells was measured by flow cytometry. The levels of P-gp, P210(bcr-abl) and p-P210(bcr-abl) protein were detected by Western blot.

RESULTSPHI inhibited proliferation and induced apoptosis of K562/G01 cells after treated with PHI alone for 24 h. PHI concentration increased from 0 to 40 µmol/L, the inhibitory rate of cell proliferation from 0 to (51.22 ± 1.41)%, and the apoptosis rate from (3.76 ± 1.46)% to (35.35 ± 3.70)%. Combination of 10, 20, 40 µmol/L PHI and various concentrations of imatinib, IC50 s of imatinib were (10.49 ± 1.24), (6.33 ± 1.42), and (0.85 ± 0.17) µmol/L, respectively. When K562/G01 cells treated with 20 µmol/L PHI combined with 10 and 20µmol/L imatinib for 24 hours, apoptosis rate were (43.62 ± 4.23)% and (55.41 ± 4.35)%, respectively, being significantly higher than that with imatinib or PHI alone. PHI concentrations increased from 0 to 40 µmol/L for 7 hours, the P210(bcr-abl)/β-actin decreased from (0.944 ± 0.034) to (0.392 ± 0.025), and the p-P210(bcr-abl)/β-actin decreased from (0.906 ± 0.019) to (0.361 ± 0.021), while the alteration of P-gp was not seen.

CONCLUSIONSPHI inhibits the proliferation and induces apoptosis of K562/G01 cell line. PHI has synergistic effect with imatinib. It partially reverses the drug-resistance to imatinib. The mechanism of reversal of drug resistance in K562/G01 cells might be by inhibiting P210(bcr-abl) and p-P210(bcr-abl).