Effects of endoplasmic reticulum stress-mediated CREB3L1 on apoptosis of glioma cells

Zhao Yan; Yaxin Hu; Yiwei Zhang; Qian Pu; Liangzhao Chu; Jian Liu

doi:10.3892/mco.2022.2516

Effects of endoplasmic reticulum stress-mediated CREB3L1 on apoptosis of glioma cells

Mol Clin Oncol. 2022 Apr;16(4):83. doi: 10.3892/mco.2022.2516. Epub 2022 Feb 15.

Authors

Zhao Yan^{1

2}, Yaxin Hu¹, Yiwei Zhang^{1

2}, Qian Pu¹, Liangzhao Chu^{1

2}, Jian Liu^{1

2

3}

Affiliations

¹ Department of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.
² Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China.
³ Department of Neurosurgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China.

Abstract

The association between endoplasmic reticulum stress (ERS) and apoptosis has been extensively studied. Cyclic adenosine monophosphate responsive element binding protein 3 like 1 (CREB3L1) has an important role in the development of glioma. In the present study, the potential association between ERS-induced apoptosis and CREB3L1 and its clinical implications were investigated. From a total of 30 cases, brain gliomas with different pathological grades surgically resected at the Department of Neurosurgery of the Affiliated Hospital of Guizhou Medical University (Guiyang, China) between January 2018 and January 2019 were collected. The expression of CREB3L1 and ERS-related proteins in gliomas with different degrees of malignancy was detected by immunohistochemistry. Furthermore, U87-MG glioma cells were cultured in vitro and treated with different concentrations of ERS inducer thapsigargin (TG). The Cell Counting Kit-8 (CCK-8) assay was performed to detect changes in cell activity at different incubation times and drug concentrations. Cell apoptosis was detected by Annexin Ⅴ-FITC/propidium iodide double staining and the protein expression levels of CREB3L1 and ERS were detected by western blot analysis. Immunohistochemical analysis suggested that the expression levels of CREB3L1, glucose-regulated protein, 78 kDa (GRP78) and C/EBP-homologous protein (CHOP) in World Health Organization (WHO) grade I glioma were higher than those in WHO grade Ⅱ-Ⅳ (all P<0.01). The results of the CCK-8 assay suggested that the activity of U87-MG glioma cells was significantly decreased after treatment with TG (all P<0.05), and this effect was time- and drug concentration-dependent. Flow cytometric analysis indicated that the apoptotic rate of the cells was increased, which was significant when the concentration of TG was 0.1 µmol/l (P<0.01). Furthermore, the protein expression of CREB3L1, GRP78 and CHOP in glioma cells treated with TG was increased (P<0.05). However, the expression level of Bcl-2 decreased (P<0.05). In conclusion, ERS may reduce the cell proliferative activity and promote apoptosis through mediating CREB3L1 expression. CREB3L1 may be a novel potential target for glioma therapy.

Keywords: CREB3L1; U87-MG; apoptosis; endoplasmic reticulum stress; glioma cells; thapsigargin.

Grants and funding

Funding: This study was funded by the National Natural Science Foundation of China (grant no. 81560409) and the Science Foundation of Guizhou Province of China [grant nos. (2014) 6008 and QianKeHe (2016) support 2905] and the Science and Technology Foundation approved by Guizhou Provincial Health Commission [no. gzwkj (2022-090)].