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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Analysis of Variance, Apoptosis, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Caspase 3, Electrophoretic Mobility Shift Assay, Flow Cytometry, Humans, NF-kappa B, Receptor, Notch1, Stomach Neoplasms, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Up-Regulation.
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Does over-activated Notch-1 protect gastric carcinoma BGC-823 cells from TNFalpha-induced apoptosis? Context: The role of Notch-1 in human gastric carcinoma, one of the most common carcinomas of the human digestive tract, remains poorly characterised. Here, we investigated the effect and mechanism of Notch-1 activation on TNFalpha-induced apoptosis of human gastric carcinoma BGC-823 cells. Cell viabililty was measured by MTT assay. Apoptosis was detected by flow cytometry assay. Notch-1, Hes-1, caspase-3 p20 and NF-kappaB p65 expressions were assayed by Western blotting. NF-kappaB activation was tested by electrophoretic mobility shift assay (EMSA), and caspase-3 activation was tested by colorimetric assay. BGC-823 cells underwent apoptosis following stimulation with TNFalpha. We found that Notch-1 was over-activated by overexpressing exogenous intracellular domain of Notch (ICN) via retrovirus-mediated gene transfer, and over-activated Notch-1 reduced the TNFalpha-induced growth suppression and apoptosis in BGC-823 cells. Down-regulation of Notch-1 by siRNA targeting Notch-1 enhanced TNFalpha-induced apoptosis in BGC-823 cells. As the molecular mechanism involved, we showed over-activated Notch-1 partially suppressed TNFalpha-induced activation of caspase-3. However, TNFalpha-induced activation of NF-kappaB was not affected by over-activated Notch-1.
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Our data indicate that over-activated Notch-1 significantly protects BGC-823 cells from TNFalpha-induced apoptosis, and this effect is mediated, at least in part, by decreasing activation of caspase-3 independent of NF-kappaB. Final Decision: yes