Involvement of GRP78 in the Resistance of Ovarian Carcinoma Cells to Paclitaxel


Background: Glucose regulated protein 78 (GRP78) is a type of molecular chaperone. It is a possible candidateprotein that contributes to development of drug resistance. We first examined the involvement of GRP78 inchemotherapy-resistance in human ovarian cancer cell. Materials and
Methods: The expression of GRP78mRNA and protein were examined by RT-PCR and western blotting, respectively, in human ovarian cancer cellsline (HO-8910). Sensitivity of HO-8910 to paclitaxel was determined with methyl thiazolyl tetrazolium (MTT).Suppression of GRP78 expression was performed using specific small-interfering RNA (siRNA) in HO-8910cells, and cell apoptosis was assessed by flow cytometry. Statistical analysis was performed using the SPSS 15.0statistical package.
Results: HO-8910 cells, with high basal levels of GRP78, exhibited low sensitivity to paclitaxel.The mRNA and protein levels of GRP78 were dramatically decreased at 24h, 48h and 72h after transfection andthe sensitivity to paclitaxel was increased when the GRP78 gene was disturbed by specific siRNA transfection.
Conclusions: The results suggested that high GRP78 expression might be one of the molecular mechanismscausing resistance to paclitaxel, and therefore siRNA of GRP78 may be useful in tumor-specific gene therapyfor ovarian cancer.