ShDcR3 sensitizes TRAIL-resistant HCC cells by inducing caspase-dependent apoptosis while suppressing NF-κB dependent cFLIPL expression.

ABSTRACT: Evidence has shown that most hepatocellular carcinoma (HCC) cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the molecular mechanisms underlying TRAIL-mediated apoptosis resistance are not well understood. In this study, we reported that downregulation of Decoy receptor 3 (DcR3) expression by lentiviral vectors carrying shRNA against DcR3 (LV-ShDcR3, shDcR3) in Huh7 both greatly enhanced TRAIL-mediated apoptosis and reduced cell proliferation capability. In addition, silencing DcR3 resulted in upregulation of the cell apoptotic regulators including Bid, caspase-3, and caspase-8. Caspase inhibitors inhibited shDcR3-mediated cell death, which indicated that downregulation of DcR3 expression in Huh7 cells increased TRAIL

SUBMITTER: Liang DY 

PROVIDER: S-EPMC5812574 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature