Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis. The results demonstrated that aspirin inhibited inflammation and apoptosis of cerebrovascular endothelial cells in a mouse model of cerebral infarction. Aspirin treatment suppressed toll‑like receptor (TLR)4 and nuclear factor (NF)‑κB expression in cerebrovascular endothelial cells. Endoplasmic reticulum (ER) stress was suppressed by aspirin treatment through the downregulation of protein kinase R‑like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2 subunit 1 and C/EBP homologous protein expression levels in cerebrovascular endothelial cells. It was identified that knockdown of TLR4 inhibited aspirin‑mediated downregulation of NF‑κB signaling pathway and ER stress in cerebrovascular endothelial cells. Expression levels of adenosine diphosphate plasminogen activator inhibitors, von Willebrand factor and thromboxane were downregulated in cerebrovascular endothelial cells and in serum in experimental mice. The results demonstrated that aspirin was beneficial forthrombolysis by decreasing thrombin‑activatable fibrinolysis inhibitor and plasminogen activator inhibitor‑1 expression in a mouse model of cerebral infarction. These results suggested that aspirin may improve cerebral infarction by downregulating TLR4/NF‑κB‑mediated ER stress in a mouse model.

BackgroundMalignant glioma is intractable primary brain carcinoma that has a poor survival rate. Natural diterpenoid isoferritin A (IsoA) presents antitumor effects by regulating signal pathways in tumor cells. In the present study we investigated the inhibitory effects of IsoA on glioma cells.Material/MethodsThe potential molecular mechanism of IsoA-mediated glioma cell growth and metastasis were investigated using Western blot, gene knockdown, immunofluorescence, and immunohistochemistry.ResultsResults showed that IsoA significantly inhibits growth and metastasis of glioma cells in multiple preclinical settings. In vitro assay showed that IsoA (4 mg/ml) treatment significantly induced apoptosis of glioma cells. Mechanism analysis demonstrated that IsoA (4 mg/ml) treatment decreased TGFβ and regulated EMT markers expression in glioma cells. Reduced expression of TGFβ in glioma cells was closely correlated with inhibitory effects of IsoA on growth and metastasis of glioma cells. TGFβ overexpression promoted glioma cell growth and invasion. Results also showed that IsoA treatment significantly decreased Fibronectin and Vimentin and increased E-cadherin, while TGFβ overexpression abolished the regulation mediated by IsoA in glioma cells. In vivo assay showed that IsoA treatment inhibited tumor growth in a glioma-bearing mouse model.ConclusionsResults indicate that IsoA could be regarded as a potential anti-cancer agent by regulating TGFβ-induced EMT signal pathway.

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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)/β-catenin in glioblastoma cells. Results also indicated that tunicamycin administration promoted the Wnt/β-catenin signaling pathway in glioblastoma cells. Knockdown of MEG-3 inhibited tunicamycin-mediated downregulation of the Wnt/β-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/β-catenin signaling, suggesting that tunicamycin may be a potential anticancer agent for glioblastoma therapy.

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