Anticancer effect of resibufogenin on gastric carcinoma cells through the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β signaling pathway

摘要

The aim of the present study was to investigate the anticancer effect of resibufogenin in gastric carcinoma cells through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) signaling pathway. MGC-803 cells were treated with 0, 1, 2, 4 and 8 µM resibufogenin for 12, 24 and 48 h. Cell viability and apoptosis were measured using an MTT assay and annexin V staining. Caspase-3 and caspase-8 activity were identified using caspase-3 and caspase-8 activity kits and a variety of protein expression [B cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), cyclin D1, cyclin E, PI3K, phosphorylated AKT, phosphorylated GSK3β and β-catenin] were quantified using western blot analysis. It was revealed that resibufogenin effectively inhibited cell proliferation, and induced apoptosis and caspase-3 and caspase-8 activity in MGC-803 cells. Furthermore, treatment with resibufogenin effectively increased Bax/Bcl-2 expression, and suppressed cyclin D1, cyclin E, PI3K, phosphorylated AKT, phosphorylated GSK3β and β-catenin protein expression in MGC-803 cells. These results suggest that the anticancer effect of resibufogenin induces gastric carcinoma cell death through the PI3K/AKT/GSK3β signaling pathway, offering a novel view of the mechanism by which resibufogenin functions as an agent to treat gastric carcinoma.