Role of the phosphatidylinositol 3'-kinase-Akt signal pathway in the proliferation of human pancreatic ductal carcinoma cell lines

Pancreas. 2004 Apr;28(3):353-8. doi: 10.1097/00006676-200404000-00026.

Abstract

: Phosphatidylinositol 3'-kinase (PI3K) and Akt mediate survival signals and allow the cells to escape apoptosis in various human cancers. We postulated that LY294002, a PI3K inhibitor, might inactivate Akt, consequently inhibiting cell proliferation in 3 human pancreatic ductal carcinoma cell lines, PSN-1, PANC-1, and KP-4. LY294002 (50 micromol/L) caused a decrease in phosphorylated Akt and inhibition of cell proliferation in a time-dependent manner, but there was no obvious induction of apoptosis. Flow cytometric analysis revealed that pancreatic cancer cells treated with 50 micromol/L LY294002 underwent G1 arrest, which was associated with dephosphorylation of the ppRB protein, a decrease in the protein expression of cyclin D and E, and their activating partners Cdk2, 4, and 6 with simultaneous accumulation of P27/Kip1. Our data indicate that P27/Kip1 accumulation by Akt inactivation could induce cell cycle arrest in the G1 phase and suggest that the PI3K-Akt pathway plays an important role in cell proliferation in human pancreatic ductal carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Pancreatic Ductal / enzymology*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Morpholines / pharmacology
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction* / drug effects

Substances

  • Cell Cycle Proteins
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt