The inhibition of Bid expression by Akt leads to resistance to TRAIL-induced apoptosis in ovarian cancer cells.

ABSTRACT: Epithelial ovarian cancer (EOC) cells often show increased activity of the PI3K/Akt pathway. In addition, we have previously shown that EOC ascites induce Akt activation in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive EOC cell line, CaOV3, leading to TRAIL-mediated apoptosis inhibition. In this study, we investigated the role of Akt in intrinsic resistance to TRAIL, which is common in EOC cells. We report that Akt activation reduces the sensitivity of EOC cells to TRAIL. TRAIL-resistant SKOV3ip1 and COV2 cells were sensitized to TRAIL-induced apoptosis by PI3K or Akt inhibitors although inhibition of PI3K/Akt signaling pathway did not interfere with the recruitment and processing of caspase-8 to the death-inducing signaling complex. Conversely, overexpressi

SUBMITTER: Goncharenko-Khaider N 

PROVIDER: S-EPMC3007125 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature