Abstract: Objective To investigate the effect of arsenic trioxide（As2O3）on human osteosarcoma cells MG63 and drug resistant cells MG63／dox，and to explore its possible mechanism. Methods MG63 and MG63/dox cells were respectively treated with adriamycin（ADM, 1-1000 ng／ml）or As2O3（0.25-16 μmol／L） for 48 h; 2 μmol／L As2O3 in combination with ADM（1-1000 ng／ml）was employed to treat MG63/dox cells for 24, 48, 72 h. Meanwhile, negative control group was set. The effect of As2O3 and ADM on proliferation of MG63／dox cell were detected by CCK8 assay. The cell cycle and apoptotic rate of MG63／dox cells after treatment with As2O3（2 μmol／L）and ADM（200 ng/ml）alone and their combination for 48 h were detected by flow cytometry， and the expression levels of P-gp，Bcl-2 and Bax proteins treated by As2O3（2 μmol／L）or ADM（200 ng/ml） alone or in combination for 48 h were analyzed by Western blotting，respectively. Results As2O3 or ADM alone treated MG63/dox cells for 48 h, the proliferation of cells had no obvious changes. The concentration of 4, 8, 16 μmol/L As2O3 and 100, 200, 400, 500, 1000 ng/ml ADM respectively treated MG63 cells for 48 h, the cell proliferation was inhibited（P＜0.05）. As2O3 in combination with ADM markedly inhibited cell proliferation in MG63／dox cells compared with ADM group and control group（P＜0.05）in timedependent manner. Compared with the control group，As2O3 in combination with ADM increased the apoptosis of MG63／dox cells and G2／M phase cell cycle arrest, but reduced G0/G1 phase cell arrest（P＜0.05）. Furthermore，the expression of Bax protein was found to be upregulated in MG63／dox cells，and the expressions of P-gp and Bcl-2 proteins were lower than those in control group（P＜0.05）. Conclusion As2O3 combined with ADM can inhibit the proliferation of MG63／dox cells. This effect may associate with induction of apoptosis，up-regulation of Bax expression and down-regulation of P-gp and Bcl-2 expressions.