Over-expression of NOTCH-1 inhibits TNF?-induced apoptosis and proliferation suppression in human gastric carcinoma cells / 基础医学与临床

ABSTRACT

Objective To explore the regulatory function of over-expression of NOTCH-1 in TNF?-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 screening with G-418.Before and after incubation with TNF?,MTT assay,flow cytometry,Western blot and EMSA were used to detect cell growth,apoptosis,expressions of NOTCH-1,NF-?B 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 TNF? treatment,the rates of killing and apoptosis in NOTCH-1-transfected cells were all lower than those in control cells.Moreover,we showed over-expression of NOTCH-1 suppressed caspase-3 activation induced by TNF?.However,TNF?-induced activation of NF-?B was not affected by over-expression of NOTCH-1.Conclusion Over-expression of NOTCH-1 significantly protects BGC-823 cells from apoptosis and growth suppression induced by TNF?.This effect is mediated,at least in part,through inhibition of caspase-3 activation independent of NF-?B.