Impairment of Both Apoptotic and Cytoprotective Signalings in Glioma Cells Resistant to the Combined Use of Cisplatin and Tumor Necrosis Factor α

摘要: Purpose: Tumor necrosis factor (TNF)-α elicits two opposing effects, the induction of apoptosis and transcription antiapoptotic genes. We have recently shown that cisplatin sensitizes glioma cells to TNF-induced apoptosis, but only in some cell lines. To understand mechanism involved different susceptibilities, we examined both activation caspases cytoprotective signaling by TNF-α. Experimental Design: Caspase was estimating cleavage substrate peptides immunoblot identify procaspases. Peptide inhibitors were used reverse cytotoxicity. The binding TNF-α receptor analyzed flow cytometry. Nuclear (NF)-κB assayed NF-κB oligonucleotides containing consensus site. Interleukin (IL)-1β, IL-6, IL-8, manganous superoxide dismutase (MnSOD) measured enzyme-linked immunoassays. Results: T98G U87MG underwent on treatment with TNF-α, U373MG A172 resistant. Caspases 2, 3, 6–10, not 1, 4, 5, activated sensitive cells, none resistant cells. same all four In production IL-1β, MnSOD significantly elevated However, IL-1β IL-6 specifically impaired response Conclusions: Our results indicate apoptotic pathways are