Targeting GRP78 as a Basis for Enhanced Glioma Cells Killing by Anti-TfR Antibody

Özet

AIM: Studies have illustrated that chemotherapeutic drugs induce endoplasmic reticulum (ER) stress in glioblastoma cells. In ourprevious studies, it is clear that anti-transferrin receptor (anti-TfR) monoclonal antibody (mAB) 7579 enhanced anti-tumor effects ofchemotherapeutic drugs on human glioma cells in vitro. In our study, we therefore investigated how the anti-TfR antibody increasedER stress, alone or in combination with a chemotherapeutic drug.MATERIAL and METHODS: ER stress was detected after cells were treated with anti-TfR mAb and/or Nimustine by westernblot analysis. The colony survival and apoptosis of cells were detected after transfection with small interfering RNA (siRNA) andtreatment with anti-TfR mAb and/or Nimustine by labeling with methylene blue and FCM.RESULTS: The anti-TfR antibody combined with Nimustine could elevate expression of GRP78/BiP and CHOP/GADD153 andfurther increase ER stress. SiRNA against the ER stress marker GRP78 produced a further sensitization of glioma cells to killing bythe anti-TfR antibody and/or Nimustine.CONCLUSION: Our results show the anti-TfR antibody triggers the ER stress response. Furthermore, this anti-tumor effect isachieved via the siRNA against GRP78 for glioma cell growth and its survival. These results hold promise as a clinical approach togene therapy for malignant gliomas.