Abstract: Objective To investigate the effect of small interfering RNA-mediated glucose-regulated protein 78 (GRP78)
knockdown on the chemosensitivity of breast cancer cells to cisplatin. Methods Human breast cancer cell line MDA-MB-231
was exposed to different doses of cisplatin (0, 1, 2, 4, 8, and 16 μmol/L), and the changes in cell viability were detected using
MTT assay. PI/Annexin V staining was used to observe the apoptosis of the cells in response to transfection with a small
interfering RNA targeting GRP78 (pSH1Si-GRP78). Western blotting was employed to detect GRP78 expression in pSH1Si-
GRP78-transfected cells after exposure to 8 μmol/L cisplatin for 24, 48 and 72 h. Results Exposure of the cells to 8 μmol/L
cisplatin for 24, 48 and 72 h resulted in a cell survival rate of 83.13%, 54.22% and 35.79%, respectively, but the cell apoptosis
rate was only 10.8% at 24 h. Transfection of MDA-MB-231 cells with pSH1Si-GRP78 caused a cell apoptosis rate of 24.6%,
which increased to 48.9% in cells with both pSH1Si-GRP78 transfection and cisplatin exposure. Cisplatin exposure caused an
initial up-regulation followed then by a down-regulation of GRP78 expression in MDA-MB-231 cells, while pSH1Si-GRP78
transfection produced an obvious down-regulation of GRP78 expression. Conclusions Inhibition of GRP78 expression
increases the apoptosis and enhance cisplatin chemosensitivity of breast cancer cells in vitro, suggesting the value of GRP78 as
a potential therapeutic target in the clinical treatment of breast cancer.