Title:Higher Levels of Dynamin-related Protein 1 are Associated with Reduced Radiation Sensitivity of Glioblastoma Cells
VOLUME: 17 ISSUE: 4
Author(s):Wen-Yu Cheng, Kuan-Chih Chow, Ming-Tsang Chiao, Yi-Chin Yang and Chiung-Chyi Shen*
Affiliation:Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Agricultural Biotechnology Centre, National Chung Hsing University, Taichung, Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung
Keywords:DRP1, glioblastoma multiforme, radiation resistance, autophagy, dNA repair, nuclear transport.
Abstract:
Background: Dynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial
fission, mitochondrial protein import, and drug sensitivity, suggesting an association with cancer
progression. This study was conducted to evaluate the prognostic significance of DRP1 in glioblastoma
multiforme (GBM).
Methods: DRP1 expression was measured by immunohistochemistry and Western blotting. Correlations
between DRP1 expression and clinicopathological parameters were determined by statistical
analysis. Differences in survival were compared using the log-rank test. DRP1 expression was
detected in 87.2% (41/47) of the investigated patients with GBM.
Results: The patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, the silencing
of DRP1 reduced cell proliferation, invasive potential, and radiation resistance. The addition of
shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear
entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that
reducing DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM
cells.
Conclusion: Our results indicate that DRP1 overexpression is a prospective radio-resistant phenotype
in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation
therapy.
