Blocking of PI3K/AKT induces apoptosis by its effect on NF-κB activity in gastric carcinoma cell line SGC7901.
NF-κB plays an important role in many aspects of tumorigenesis and tumor progression by its antiapoptosis effect. Hence, NF-κB has been regarded as a therapeutic target in cancer, because inhibition of NF-κB not only induces enhancing apoptosis but also causes increasing sensitivity to radiation or chemotherapy in several tumor cells. The activation of NF-κB 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-κB activity with significantly increased apoptosis in gastric cancer cell. Furthermore, when the cells were pretreated with IKK siRNA and/or IκB 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-κB activity is associated with the influence of PI3K/AKT on IKK/IκB. The apoptosis induced by blocking PI3K/AKT might be ascribed to inhibition of NF-κB activity through IKK/IκB at least in part.
Chao
Xu
X
Department of Oncology, Zhong-Da Hospital, Southeast University, 87 Ding-Jia-Qiao Road, Nanjing 210009, PR China.
Zao
Jiang
J
Xiao-Yi
Gu
G
Li-Jun
Meng
M
Tao
Shi
S
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D002867:Chromones; D004791:Enzyme Inhibitors; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C083487:I kappa B beta protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one