Correlation between TRAIL and caspase-8 expression and their relationship with cell proliferation and apoptosis in human osteosarcoma

Abstract

ABSTRACT. Osteosarcoma is a common malignant bone tumor that mainly affects children and adolescents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily. Caspase-8 appears in the upstream of apoptosis signaling pathway among caspases. We investigated TRAIL and caspase-8 levels in osteosarcoma patients to determine their correlation with cell proliferation and apoptosis. Osteosarcoma and osteochondroma patients receiving surgery in our hospital were selected. TRAIL and caspase-8 expression levels in tissue were determined by immunohistochemistry, and protein levels in cells were evaluated by western blotting. Human osteosarcoma cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The osteosarcoma and osteochondroma cell cycles and apoptosis were investigated by flow cytometry. Correlation analysis was applied to TRAIL and caspase-8 levels during cell apoptosis. Positive TRAIL and caspase-8 expression rates in osteosarcoma tissue were significantly lower than in the controls (P < 0.05). TRAIL (0.114 ± 0.002) and caspase-8 (0.352 ± 0.124) levels in experimental cells were obviously lower than in the controls (P < 0.05). Osteosarcoma cells in the experimental group demonstrated higher proliferation and lower apoptosis at 24, 48, and 72 h (P < 0.05). The experimental cell number increased in the G1 stage and decreased in the S stage (P < 0.05). TRAIL and caspase-8 proteins showed positive correlation with apoptosis in osteosarcoma (P < 0.05). Human osteosarcoma presented reduced TRAIL and caspase-8 levels with enhanced cell proliferation and reduced apoptosis. TRAIL and caspase-8 expression levels were positively correlated with apoptosis in osteosarcoma.

The Relationship of Pyroptosis-Related Genes, Patient Outcomes, and Tumor-Infiltrating Cells in Bladder Urothelial Carcinoma (BLCA)

“…Furthermore, the relationship between CASP8, patient survival, TICs, and ICPIs as demonstrated by our data may open new avenues for treatment of BLCA, making CASP8 an attractive therapeutic target ( Stupack, 2013 ). For instance, one important way to activate CASP8-related apoptosis is by engaging the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; TNFSF10)-receptor, which could mediate CASP8-related apoptosis ( Ning et al, 2016 ).…”