Dataset Information

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.

ABSTRACT: Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo. Furthermore, borneol markedly increased the number of autophagosomes in the glioma cells, which coincided with increased expression of beclin-1 and LC3. And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E. In addition, silencing mTORC1 and eIF4E upregulated Beclin-1 and LC3 and decreased the expression of HIF-1α, thereby inhibiting tumor cell proliferation. Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.

SUBMITTER: Li Q

PROVIDER: S-EPMC8668811 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.

Li Qinglin Q Xia Liang L Sun Caixing C Zhang Huangjie H Zheng Mengying M Zhang Hongyan H Lu Hongyang H Wang Zeng Z

Frontiers in oncology 20211130

Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells <i>in vi ...[more]

PMID: 34917504

Similar Datasets

Project description:BackgroundMalignant glioma is rarely curable, and factors that inﬂuence the prognosis of glioma patients are not fully understood. Lysyl hydroxylases such as PLOD1 promote the cross-linking in extracellular matrix (ECM) molecules, which contribute to ECM structural stability and maturation. However, the expression and prognostic role of PLOD1 in malignant glioma remained to be determined.MethodsThe expression of PLOD1 was evaluated by immunohistochemistry in 72 malignant glioma patients from Shenzhen People's hospital. The mRNA expression profiles and clinical information of malignant glioma patients were obtained from public databases, including TCGA, CGGA, Rembrandt, and Gravendeel. The correlation between gene expression and tumor grade, and IDH1/2 status and 1p19q status were evaluated. The association between gene expression and overall survival of malignant glioma patients was examined using Kaplan-Meier survival analysis. GO and KEGG pathways were analyzed by Metascape. Transwell invasion assays were performed to determine the effect of PLOD1 on migration and invasion of glioma cells in vitro.ResultsPLOD1 expression was significantly elevated in malignant glioma tissues compared with non-tumor brain tissues. Besides, elevated levels of PLOD1 were significantly correlated with high tumor grade, wildtype IDH1/2 status, and 1p19q non-codel in all the four public datasets and in-house cohort. Malignant glioma patients with high PLOD1 expression had better overall survival compared to those with low PLOD1 expression. More importantly, patients with IDH1/2 mutations, 1p19q codeletions, and PLOD1 overexpression had the best overall survival. GO enrichment pathway analysis indicated that PLOD1 participates in regulating the extracellular matrix. Transwell invasion assay, which revealed that inhibiting PLOD1 reduced cell invasion in both U87 and U251 cells.ConclusionPLOD1 serves as a potential prognostic marker and therapeutic target for malignant glioma.

Project description:OBJECTIVE:Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. METHODS:We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC50 radiation dose was determined. Dexamethasone dose (10 μM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. RESULTS:Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. CONCLUSION:Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTEN-mutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

Dataset Information

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.

Publications

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets