Increased expression of GRP94 protein is associated with decreased sensitivity to X-rays in cervical cancer cell lines.

Purpose: Radiation therapy is one of the standard treatments for cervical cancer. Glucose regulated protein 94 (GRP94) is a molecular chaperone, which increases in amount after X-ray irradiation. This study examined the involvement of GRP94 in radio-resistance in human cervical cancer cells.

Materials And Methods: Seven human cervical carcinoma cell lines (HeLa, SKG-I, SKG-IIIb, QG-U, Caski, SiHa and C33A) were examined for basal levels of GRP94 protein by western blotting analysis. Sensitivity to X-ray irradiation of these cell lines was determined with a colony survival assay. The suppression of GRP94 expression was performed using specific small-interfering RNA (siRNA) in HeLa and Caski cells.

Results: HeLa cells and QG-U cells, with higher basal levels of GRP94, exhibited a low sensitivity to X-ray cell killing. In HeLa cells, the sensitivity increased when protein GRP94 levels were reduced by specific siRNA transfection. However, a reduction in GRP94 protein had little effect on the X-ray sensitivity of Caski cells, which expressed low basal GRP94 protein levels but showed a low sensitivity to X-rays.

Conclusions: High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer.