Cell detachment modulates TRAIL resistance in ovarian cancer cells by downregulating the phosphatidylinositol 3- kinase/Akt pathway. Issue 4 (1st July 2008)

• Record Type: Journal Article
• Authors: Lane, D.; Cartier, A.; Rancourt, C.; PichÉ, A.
• Is Part Of: International journal of gynecological cancer. Volume 18:Issue 4(2008)
• Page Start: 670
• Page End: 676
• Publication Date: 2008-07-01
• Subjects: apoptosis -- cell adhesion -- ovarian cancer -- PI3K/Akt pathway -- TRAIL; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-00009577-200807000-00011
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : 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.