Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo

J Exp Clin Cancer Res. 2010 Apr 22;29(1):34. doi: 10.1186/1756-9966-29-34.

Abstract

Background: To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells.

Methods: The activation of the PI3K/Akt and its effect on CNE-2Z cells in vivo and in vitro was investigated by MTT assay, flow cytometry, western blot, ELISA, terminal deoxyribonucleotide transferase-mediated nick-end labeling assays (TUNEL), and immunohistochemical analyses, using PI3K inhibitor, LY294002.

Results: The results showed that LY294002 inhibited the phosphorylating of Akt (S473), cell proliferation, and induced apoptosis in CNE-2Z cells. However, our experiment results also demonstrated that apoptosis-induced LY294002 was directly regulated by caspase-9 activation pathway.

Conclusion: These data suggested that PI3K inhibitor, LY294002, induced apoptosis by caspase-9 activation pathway and might be as a potentially useful target for therapeutic intervention in nasopharyngeal carcinoma patients.

MeSH terms

  • Animals
  • Apoptosis*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology*
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Chromones / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Morpholines / pharmacology*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism

Substances

  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Caspase 9