Turkish Neurosurgery 2018 , Vol 28 , Num 4
Targeting GRP78 as a Basis for Enhanced Glioma Cells Killing by Anti-TfR Antibody
Xue WEN1,Xuan CHEN1,Xiaoping CHENG1,Si WU1
1Hubei Polytechnic Institute, School of Nursing, Department of Basic Medical, Xiaogan, China DOI : 10.5137/1019-5149.JTN.20339-17.1 AIM: Studies have illustrated that chemotherapeutic drugs induce endoplasmic reticulum (ER) stress in glioblastoma cells. In our previous studies, it is clear that anti-transferrin receptor (anti-TfR) monoclonal antibody (mAB) 7579 enhanced anti-tumor effects of chemotherapeutic drugs on human glioma cells in vitro. In our study, we therefore investigated how the anti-TfR antibody increased ER 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 western blot analysis. The colony survival and apoptosis of cells were detected after transfection with small interfering RNA (siRNA) and treatment 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 and further increase ER stress. SiRNA against the ER stress marker GRP78 produced a further sensitization of glioma cells to killing by the anti-TfR antibody and/or Nimustine.

CONCLUSION: Our results show the anti-TfR antibody triggers the ER stress response. Furthermore, this anti-tumor effect is achieved via the siRNA against GRP78 for glioma cell growth and its survival. These results hold promise as a clinical approach to gene therapy for malignant gliomas. Keywords : Endoplasmic reticulum, Glioma, Glucose-regulated protein 78, Transferrin receptor

Corresponding author : Xue WEN, wenxue791203@163.com