Targeting GRP78 as a Basis for Enhanced Glioma Cells Killing by anti-TfR antibody.

AIM: Studies have shown that chemotherapeutic drugs induced endoplasmic reticulum (ER) stress in glioblastoma cells. In our previous study, we have demonstrated anti-TfR monoclonal antibody 7579 enhanced the anti-tumor effects of chemotherapeutic drugs on human glioma cells in vitro. In our study, we therefore investigated whether the anti-TfR antibody alone or the combination of anti-TfR antibody with chemotherapeutic drug would lead to increased ER stress.

MATERIAL AND METHODS: We detected ER stress after cells were treated with anti-TfR mAb or/and Nimustine by western blot analysis. We detected the colony survival and apoptosis of cells after transfection with siRNA and treated with anti-TfR mAb or/and Nimustine by lableing with methylene blue and FCM.

RESULTS: The anti-TfR antibody could elevate expression GRP78/BiP and CHOP/GADD153 and lead to further increased ER stress when combined with Nimustine. Small interfering RNA (siRNA) against the ER stress marker GRP78 further sensitized the glioma cells to killing by the anti-TfR antibody or/and Nimustine.

CONCLUSION: Our results show that the anti-tumor effects of anti-TfR antibody trigger the ER stress response, and that this effect is achieved via the siRNA against GRP78 for glioma cell growth and survival. These results hold promise as a clinical approach to gene therapy for malignant gliomas.