Abstract: Objective To explore the regulative function of over-expression of NOTCH-1 in TNFα-induced apoptosis of gastric carcinoma carcinoma BGC-823 cells. Methods BGC-823 cells were infected with retrovirus recombined with intracellular domain of NOTCH-1.The cell clones, into which objective genes had been transfected, were obtained after being screened with G-418. Before and after incubated with TNFα, MTT assay, flow cytometry,Western blot and EMSA were used to detect cell growth, apoptosis, expressions of NOTCH-1, NF-κB and caspase-3 activity. Results There was stronger expression of NOTCH-1 and its target gene HES-1 in the cells transfected with NOTCH-1 gene than that of control. After TNFα treatment, the rates of killing rates and apoptosis in NOTCH-1-transfected cells were all lower than control cells. Moreover, we showed over-expression of NOTCH-1 suppressed caspase-3 activation induced by TNFα. However, the TNFα-induced activation of NF-κB was not affected by over-expression of NOTCH-1. Conclusions over-expression of NOTCH-1 significantly protects BGC-823 cells from apoptosis and growth suppression induced by TNFα. This effect is mediated, at least in part, through inhibition of caspase-3 activation independent of NF-κB.

Key words: gastric carcinoma, apoptosis, Notch-1, caspase-3