MEK/ERK和PI3K/Akt信号通路参与调节肿瘤细胞对TRAIL敏感性的研究

In order to investigate the role of MEK/ERK and PI3K/Akt signaling pathways in regulating cell sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have conducted a comparative study regarding the effects of TRAIL on these pathways. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK/ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (U937) and TRAIL-resistant (K562) human leukemia cells. U0126 increased, but LY294002 significantly decreased TRAIL-induced apoptosis in U937 cells. We also demonstrated that ERK1/2 phosphorylation upon TRAIL treatment was obviously increased in the presence of LY294002. Overexpression of HA-Akt-WT reduced ERK1/2 phosphorylation and increased cell apoptosis induced by TRAIL. Moreover, we found that MEK/ERK and PI3K/Akt pathways had opposite effects on Bad phosphorylation upon TRAIL treatment. In conclusion, our results suggest that the crosstalk between these two pathways and the activation of ERK1/2 play crucial roles in TRAIL- induced apoptosis.