Glucose-Related Protein 78 Expression and Its Effects on Cisplatin-Resistance in Cervical Cancer

BACKGROUND: GRP78, the 78-kDa glucose-regulated protein, occupies a significant position in endoplasmic reticulum stress. Emerging evidences have shown that GRP78 induces chemoresistance in several tumors; however, the role of GRP78 in cervical cancer (CVC) still needs to be elucidated clearly. MATERIAL/METHODS: In the present study, we evaluated the expression levels of GRP78 in CVC tissues collected from patients through immunocytochemistry, western blot, and real-time PCR. To explore the exact role of GRP78 in CVC cells in the presence of cisplatin, we generated GRP78 knockdown CVC cells through small interfering RNA. After transfection, the apoptosis rate was assessed by flow cytometry. Then the expression levels of caspase-3, CHOP, and Bcl-2 in GRP78 knockdown cells were determined by western blot. RESULTS: The GRP78 levels in CVC tissues were increased significantly. Three types of CVC cells HeLa, SiHa, and C33A were treated with different concentrations of cisplatin and cultured for 12 hours, 24 hours, and 48 hours respectively. And SiHa cells exhibited the highest resistance to cisplatin at all time. Specifically, after 25 μM cisplatin treatment, more than 80% of C33A cells underwent apoptosis, whereas the apoptotic rate of SiHa cells was only 30–40%. Data suggested that GRP78 silencing increased chemo-sensitivity and improved the effects of cisplatin-induced apoptosis in SiHa cells. Moreover, inhibition of GRP78 could upregulate caspase-3 and CHOP expression and downregulate Bcl-2 expression. CONCLUSIONS: GRP78 may represent a key bio-marker of CVC and silencing GRP78 may strengthen the resistance against cisplatin. GRP78 may be a potential molecular target for CVC therapies in future.