Higher levels of dynamin-related protein 1 are associated with reduced radiation sensitivity of glioblastoma cells
| Autor: | Yi-Chin Yang, Ming-Tsang Chiao, Chiung-Chyi Shen, Kuan-Chih Chow, Wen-Yu Cheng |
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| Rok vydání: | 2020 |
| Předmět: |
Dynamins
Male endocrine system DNA repair Cell Survival Biology Radiation Tolerance Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience DNM1L 0302 clinical medicine Radiation sensitivity Developmental Neuroscience Cell Line Tumor medicine Biomarkers Tumor Gene silencing Humans Aged Cell growth Brain Neoplasms Cancer Middle Aged medicine.disease Blot Neurology 030220 oncology & carcinogenesis Cancer research Mitochondrial fission Female Glioblastoma 030217 neurology & neurosurgery |
| DOI: | 10.21203/rs.2.18627/v3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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