AIM:To study the synergistic effects of calmodulin (CaM)antagonist O-4-ethoxyl-butyl-berbamine (EBB) and pegylatedliposomal doxorubicin (PLD) on hepatoma-22 (H_(22)) in vivo.METHODS:Hepatoma model was established in 50 Balb/cmice by inoculating H_(22) cells (2.5×10~6) subcutaneously intothe right backs of the mice.These mice were divided into5 groups,and treated with saline only,PLD only,doxorubicin(Dox) only,PLD plus EBB and Dox plus EBB,respectively.In the treatment groups,mice were given 5 intravenous ofPLD or Dox on days 0,3,6,9 and 12.The first dosage of PLDor Dox was 4.5 mg/kg,the other 4 injections was 1 mg/kg.EBB (5 mg/kg) was coadministered with PLD or Dox in thecorresponding groups.The effect of drugs on the life spansof hepatoma-bearing mice and tumor response to the drugswere recorded.Dox levels in the hepatoma cells weremeasured by a fluorescence assay.Light microscopy wasperformed to determine the histopathological changes inthe major organs of these tumor-bearing mice.The MTTmethod was used to analyze the effect of Dox or PLD alone,Dox in combination with EBB,or PLD in combination withEBB on the growth of H_(22) cells in an in vitro experiment.RESULTS:EBB (5 mg/kg) significantly augmented theantitumor activity of Dox or PLD,remarkably prolongedthe median survival time.The median survival time was18.2 d for control group,but 89.2 d for PLD+EBB groupand 70.1 d for Dox+EBB group,respectively.However,Dox alone did not show any remarkable antitumor activity,and the median survival time was just 29.7 d.Addition ofEBB to Dox or PLD significantly increased the level ofDox in H_(22) cells in vivo.Moreover,EBB diminished livertoxicity of Dox and PLD.In vitro,EBB reduced the IC50value of Dox or PLD on H_(22) cells from 0.050+0.006 mg/L and0.054±0.004 mg/L to 0.012±0.002 mg/L and 0.013±0.002mg/L,respectively (P<0.01).CONCLUSION:EBB and liposomization could improve thetherapeutic efficacy of Dox in liver cancer,while decreasingits liver toxicity. AIM: To study the synergistic effects of calmodulin (CaM) antagonist O-4-ethoxyl-butyl-berbamine (EBB) and pegylatedliposomal doxorubicin (PLD) on hepatoma-22 in 50 Balb / cmice by inoculating H_ (22) cells (2.5 × 10 ~ 6) subcutaneously intothe right backs of the mice. These mice were divided into 5 groups, and treated with saline only, PLD only, doxorubicin (Dox) only, PLD plus EBB and Dox plus EBB, respectively.In the treatment groups, mice were given 5 intravenous of PLD or Dox on days 0, 3, 6, 9 and 12. The first dosage of PLDor Dox was 4.5 mg / kg, the other 4 injections was 1 mg / kg. EBB (5 mg / kg) was coadministered with PLD or Dox in the corresponding groups. the effect of drugs on the life spans of hepatoma-bearing mice and tumor response to the drugs were recorded. Digg levels in the hepatoma cells were meured by a fluorescence assay. Light microscopy was formed to determine the histopathological changes inthe major organs of these tumor-bearing mice. he MTTmethod was used to analyze the effect of Dox or PLD alone, Dox in combination with EBB, or PLD in combination with EBB on the growth of H 22 cells in an in vitro experiment .RESULTS: EBB (5 mg / kg) augmented theantitumor activity of Dox or PLD, remarkably prolonged the median survival time. 18.8 d for control group, but 89.2 d for PLD + EBB group and 70.1 d for Dox + EBB group, respectively. show any significant antitumor activity, and the median survival time was just 29.7 d. Addition of EBB to Dox or PLD significantly increased the level of Dox in H 22 cells in vivo. Moreover, EBB diminished livertoxicity of Dox and PLD. In vitro, EBB The IC50 value of Dox or PLD on H_ (22) cells from 0.050 + 0.006 mg / L and 0.054 ± 0.004 mg / L to 0.012 ± 0.002 mg / L and 0.013 ± 0.002 mg / L, respectively (P <0.01). CONCLUSION: EBB and liposomization could improve the therapeutic efficacy of Dox in liver cancer, while decreasingits liver toxicity.