Glucose-Regulated Protein 94 Modulates the Response of Osteosarcoma to Chemotherapy

Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods: In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results: Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS.