OBJECTIVETo investigate the reversal effect of dihydromyricetin(DMY) on drug resistance of K562/A02 cells to adriamycin and explore its possible mechanism.

METHODSK562 and K562/A02 cells were treated with DMY (5, 10, 20, 40, 60, 80 and 100 mg/L) and ADM (100-0.05 mg/L) for 48 h. The viability of K562 cells and K562/A02 cells was tested and the reversal effect of DMY on drug resistance of K562/A02 cells to adriamycin was analyzed by MTT. The relative concentration of ADM in cells was measured by flow cytometry. Protein expressions of drug resistance related genes including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), glutathione transferase π (GSTπ) and BCL-2 were measured by Western Blot.

RESULTSThe proliferation of K562 and K562/A02 cells was significantly decreased by DMY in dose-dependent manner as compared with control group (r1=0.37, r2=0.38). The ICof ADM on K562 and K562/A02 cells were 71.23±6.51 and 72.88±5.49 mg/L respectively. DMY (5, 10 and 20 mg/L) was low cytotoxicity. DMY (5, 10 and 20 mg/L) enhanced the sensitivity of K562/A02 cells to ADM in dose-dependent manner (r1=-0.62, r2=-0.71) and the reversal multiples was from 1.38 to 28.591. The relative concentrations of ADM in K562/A02 of DMY (5, 10 and 20 mg/L) group cells were significantly increased in dose-dependent manner compared with the control group (r=0.34). Compared with the control group, the expressions of drug resistance related protein P-gp, MRP1, GSTπ and BCL-2 were significantly decreased in dose-dependent manner in DMY (5, 10 and 20 mg/L) group (r1=-0.41, r2=-0.37, r3=-0.58, r=-0.46). Compared with the ADM group, the protein expressions of drug resistance related genes P-gp, MRP1, GSTπ and BCL-2 in DMY (5, 10 and 20 mg/L)+ADM group were significantly decreased in dose-dependent manner (r1=-0.55, r2=-0.41, r3 =-0.38, r4=-0.44).

CONCLUSIONDMY enhances the sensitivity of K562/A02 cells to ADM, its mechanism may be related with decrease of P-gp, MRP1, GSTπ and BCL-2 expressions.