Nuclear forkhead box O3a accumulation contributing to the proliferative suppression in liver cancer cells by PI3K/Akt signaling pathway

J Cancer Res Ther. 2018 Dec;14(Supplement):S1124-S1128. doi: 10.4103/0973-1482.204891.

Abstract

Background: Serine/threonine kinase is originally identified as an oncogene and the forkhead box transcription factor forkhead box O3a (Foxo3a) has been found to be decreased in various human cancers. In the present study, we explored the expression of Akt and FOXO3a in liver cancer cells.

Materials and methods: Akt level was detected by Western blotting analysis. Cell viability of HepG2, MHCC-97H, Bel7402, and L02 was determined by MTT assay. FoxO3a level was determined by Western blotting analysis.

Results: Akt level was significantly higher in liver cancer cell lines HepG2 and MHCC97-H, compared with the immortalized liver cell line L02. MTT assay results demonstrated that LY294002 significantly suppressed cell proliferation of HepG2 and MHCC-97H cells in a dose- and time-dependent manner. The underlying molecular mechanism was that miR-370 inhibited cell proliferation of liver cancer cells by activating FoxO3a.

Conclusion: PI3K inhibitor decreased the levels of phosphorylated FOXO3a and increased the levels of nuclear FOXO3a. It also inhibited cell proliferation of liver cancer cells partly by PI3K/Akt/FOXO3a signaling pathways.

Keywords: Akt; PI3K inhibitor; forkhead box O3a; liver cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Nucleus / pathology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Forkhead Box Protein O3 / metabolism*
  • Humans
  • Liver Neoplasms / pathology*
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Chromones
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt