Blocking of PI3K/AKT induces apoptosis by its effect on NF-κB activity in gastric carcinoma cell line SGC7901

NF-kappa B plays an important role in many aspects of tumorigenesis and tumor progression by its antiapoptosis effect. Hence, NF-kappa B has been regarded as a therapeutic target in cancer, because inhibition of NF-kappa B not only induces enhancing apoptosis but also causes increasing sensitivity to radiation or chemotherapy in several tumor cells. The activation of NF-kappa B is presumed to be associated with PI3K/Akt signal pathway in gastric carcinoma, but the underlying molecular mechanism remains unclear. Our work demonstrates that blocking PI3K/Akt by LY294002 inhibits the NF-kappa B activity with significantly increased apoptosis in gastric cancer cell. Furthermore, when the cells were pretreated with INK siRNA and/or I kappa B siRNA then exposed to LY294002, the results suggest that the regulatory significantly increased apoptosis in gastric cancer cell. Furthermore, when the cells were pretreated, effect of PI3K/AKT on NF-kappa B activity is associated with the influence of PI3K/AKT on IKK/I kappa B. The apoptosis induced by blocking PI3K/AKT might be ascribed to inhibition of NF-kappa B activity through IKK/I kappa B at least in part. (C) 2010 Elsevier Masson SAS. All rights reserved.