AIM To study the effect of a varyingconcentrations of arsenic trioxide on humanhepatoma cell line BEL-?402 cultured in vitro andits mechanism of action.METHODS The BEL-7402 cells were treatedwith arsenic trioxide(at the concentrations of0.5,1,2 μmol/L,respectively)for 4 successivedays.The cell growth and proliferation wereobserved by cell counting and cell-growth curve.Morphologic changes were studied withelectronmicroscopy.Flow cytometry was usedto assay celI-DNA distribution and the proteinexpression of Bcl-2 and Bax detected byimmunocytochemical method.RESULTS The cell growth was significantlyinhibited by varying concentrations of arsenictrioxide as revealed by cell counting and cell-growth curve,which was dose- and time-dependent.Arsenic trioxide treatment at 0.5,1and 2 μmol/L resulted in a sub-G1 cell peak,theapoptosis rate of the control group was 9.31%and that of 0.5 μmol/L arsenic trioxide 15.53%,no significant difference was seen between thetwo.The apoptosis rates of 1,2 μmol/L arsenictrioxide were 19.10% and 21.87% respectively,which were much higher(both P<0.05).Decrease of G_0/G_1 phase cells and increase of Sphase cells were observed by flow cytometry,suggesting the inhibition effect of 0.5,1,2 μmol/L arsenic trioxide on BEL-7402 cell lay in the G_0/G_1 phase.Morphologic changes such asintact cell membrane,nucleic condensation,apoptotic body formation were seen undertransmission electronmicrescopy,whereas the0.5 mol/L arsenic trioxide-treated BEL-7402cells showed decrease of nucleocytoplasmicratio,round nucleus,well-differentiatedorganelles in the cytoplasm.The processes andmicrovilli on the cell surface of the experimentalgroups under scanning electron microscopy weresignificantly decreased.High expressions ofBcl-2 and Bax were detected in 1 and 2 μmol/Larsenic trioxide-treated cells,these were 46%,87.33% and 83.08%,95.83% respectively,among which that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/Lresulted in a higher expression level of Bcl-2 andlower expression level of Bax,which were8.81% and 3.83% respectively,as comparedwith that of the control group(15.33%)(P_1<0.01,P_2<0.01).CONCLUSION Arsenic trioxide not onlyinhibited proliferation but also induced apoptosisof human hepatoma cell line BEL-7402.Theinduced-apoptosis effect of 1,2 μmol/L arsenictrioxide was related to the expression level ofBcl-2 and Bax. The AIM To study the effect of a varyingconcentrations of arsenic trioxide on humanhepatoma cell line BEL-?402 cultured in vitro andits mechanism of action.METHODS The BEL-7402 cells were treated with arsenic trioxide(at the concentrations of0.5,1,2 μmol/ L,respectively for 4 Nextdays.The cell growth and proliferation wereobserved by cell counting and cell-growth curve.Morphologic changes were studied withelectronmicroscopy.Flow cytometry was usedto assay celI-DNA distribution and the protein expression of Bcl-2 and Bax detected byimmunocytochemical method .RESULTS The cell growth was significantlyinhibited by varying concentrations of arsenictrioxide as indicated by cell counting and cell-growth curve, which was dose- and time-dependent.Arsenic trioxide treatment at 0.5,1 and 2 μmol/L resulted in a sub-G1 cell Peak,theapoptosis rate of the control group was 9.31%and that of 0.5 μmol/L arsenic trioxide 15.53%,no significant difference was seen between thetwo.The apoptosis rates of 1,2 μ Mol/L arsenic trioxide were 19.10% and 21.87% respectively,which were much higher(both P<0.05).Decrease of G_0/G_1 phase cells and increase of Sphase cells were observed by flow cytometry,suggesting the inhibition effect of 0.5,1, 2 μmol/L arsenic trioxide on BEL-7402 cell lay in the G_0/G_1 phase. Morphologic changes such asintact cell membrane, nuclear condensation, apoptotic body formation were seen undertransmission electronmicrescopy, whereas the 0.5 mol/L arsenic trioxide-treated BEL- 7402cells decreased decrease in nucleocytoplasmicratio, round nucleus, well-differentiated organs in the cytoplasm.The processes and microvilli on the cell surface of the experimentalgroups under scanning electron microscopy weresignificantly decreased.High expressions of Bcl-2 and Bax were detected in 1 and 2 μmol/Larsenic trioxide -treated cells,these were 46%,87.33% and 83.08%,95.83% respectively,among which that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/Lresulted in a higher expre SsionLevel of Bcl-2 andlower expression level of Bax, which were8.81% and 3.83% respectively,as compared with that of the control group(15.33%)(P_1<0.01,P_2<0.01).CONCLUSION Arsenic trioxide not only inhibited proliferation but also The induced apoptosis of human hepatoma cell line BEL-7402.The induced-apoptosis effect of 1,2 μmol/L arsenic trioxide was related to the expression level of Bcl-2 and Bax.