MEG-3-mediated Wnt/β-catenin signaling pathway controls the inhibition of tunicamycin-mediated viability in glioblastoma

被引:5
|
作者
Cui, Xiangyu [1 ]
Sun, Dezhou [1 ]
Shen, Bin [1 ]
Wang, Xin [1 ]
机构
[1] Dezhou Peoples Hosp, Dept Neurosurg, 1751 Xinhuda St, Dezhou 253045, Shandong, Peoples R China
关键词
tunicamycin; glioblastoma; maternally expressed gene-3; wingless; integrated/beta-catenin; aggressiveness; APOPTOSIS-INDUCING LIGAND; ENDOPLASMIC-RETICULUM STRESS; HUMAN PROSTATE-CANCER; GLIOMAS; CELLS; THERAPY; TARGET; COMBINATION; PROGRESSION; MODELS;
D O I
10.3892/ol.2018.9048
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioblastoma is the most common primary brain carcinoma and leads to a poor survival rate of patients worldwide. Results of previous studies have suggested that tunicamycin may inhibit aggressiveness by promoting apoptosis of glioblastoma cells. In the present study, the effects of tunicamycin and its potential molecular mechanisms underlying the viability and aggressiveness of glioblastoma cells were investigated. Western blot analysis, the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, apoptosis assays and immunofluorescence were employed to examine the effects of tunicamycin on apoptosis, viability, aggressiveness and cell cycle arrest of glioblastoma cells by downregulation of the expression levels of fibronectin and epithelial cadherin. In vitro experiments demonstrated that tunicamycin significantly inhibited the viability, migration and invasion of glioblastoma cells. Results demonstrated that tunicamycin administration promoted apoptosis of glioblastoma cells through the upregulation of poly(ADP-ribose) polymerase and caspase-9. Cell cycle assays revealed that tunicamycin suppressed the proliferation of, and induced cell cycle arrest at S phase in, glioblastoma cells. Additionally, tunicamycin increased the expression of maternally expressed gene-3 (MEG-3) and wingless/integrated (Wnt)/-catenin in glioblastoma cells. Results also indicated that tunicamycin administration promoted the Wnt/-catenin signaling pathway in glioblastoma cells. Knockdown of MEG-3 inhibited tunicamycin-mediated downregulation of the Wnt/-catenin signaling pathway, which was inhibited further by tunicamycin-mediated inhibition of viability and aggressiveness in glioblastoma. In vivo assays demonstrated that tunicamycin treatment significantly inhibited tumor viability and promoted apoptosis, which further led to an increased survival rate of tumor-bearing mice compared with that of the control group. In conclusion, these results indicate that tunicamycin may inhibit the viability and aggressiveness by regulating MEG-3-mediated Wnt/-catenin signaling, suggesting that tunicamycin may be a potential anticancer agent for glioblastoma therapy.
引用
收藏
页码:2797 / 2804
页数:8
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