Abstract: Objective:To study the effect of down-regulating glucose regulated protein 78 (GRP 78) on adriamycin (ADR) induced apoptosis in human breast cancer cell line SK-BR-3,and to provide a new target for chemotherapy of breast cancer.Methods:Human breast cancer cell line SK-BR-3 cells were cultured,and treated with ADR (1 mg/L) for 0,6,12,24,and 36 hours;the expression of GRP78 at different time points was measured by Western blot.After treated with ADR for 48 hours,SK-BR-3 cells were harvest and stained with propidium iodide for apoptotic assay.SK-BR-3 cells were pretreated with siRNA,and the same was done to ADR;cell apoptosis was measured to compare the effect of GRP78 on ADR induced apoptosis in SK-BR-3.Results:ADR induced ER stress and up-regulated the expression of GRP78.ADR induced less than 30% cell apoptosis in SK-BR-3 cells.siRNA significantly blocked the expression of GRP78 and increased the apoptosis induced by ADR.The apoptosis rate was (62.30±0.88)% (P<0.01).Conclusions:Inhibition of the expression of GRP78 in human breast cancer cells SK-BR-3 can increase the sensitivity of ADR-induced apoptosis through ER pathway,which may promote the apoptosis of tumor cells and enhance the anti-tumor effect.