Article Text

Download PDFPDF
Cell detachment modulates TRAIL resistance in ovarian cancer cells by downregulating the phosphatidylinositol 3- kinase/Akt pathway
  1. D. Lane,
  2. A. Cartier,
  3. C. Rancourt and
  4. A. PichÉ
  1. Dé partement de microbiologie et infectiologie, Faculté de mé decine, Université de Sherbrooke, Sherbrooke, Qué bec, Canada
  1. Address correspondence and reprint requests to: Alain Piché, MD, MSc, Dé partement de Microbiologie et Infectiologie, Université de Sherbrooke, 3001, 12iè me Avenue Nord, Sherbrooke, Qué bec, Canada J1H 5N4. Email: alain.piche{at}


TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis but many ovarian cancer cells display intrinsic resistance to TRAIL. The molecular determinants regulating TRAIL sensitivity in these resistant tumor cells are still incompletely understood. We observed that cell detachment enhances TRAIL-induced apoptosis in two TRAIL-resistant ovarian cancer cell lines. This process was accompanied by an increase of caspase activation, which could be blocked by caspase-8 inhibitor IETD. Cell detachment inhibited Akt phosphorylation. Phosphatidylinositol 3-kinase inhibition by LY294002 also enhanced TRAIL-induced apoptosis. Further decreased Akt activity by LY294002 in detached cells translated to increased cell death after TRAIL treatment. Our data indicate that cell detachment enhances TRAIL-induced killing by decreasing Akt activity in TRAIL-resistant ovarian carcinoma cells and suggest that Akt inhibition primes TRAIL-resistant cells to TRAIL-induced apoptosis.

  • apoptosis
  • cell adhesion
  • ovarian cancer
  • PI3K/Akt pathway

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.