Abstract
15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) plays an important role in cell proliferation and apoptosis with various inhibitory effects. We investigated whether 15d-PGJ2 influence proliferation and apoptosis of human microvascular endothelial cells (HMEC-1), and suppression of the nuclear factor (NF)-κB activity and PI3K/AKT/mTOR signal pathway. Cell proliferation was analyzed using the MTS/PMS and colony formation assays. We analyzed the cell cycle using flow cytometry, while quantitative polymerase chain reaction (qPCR) measured mRNA expression, and immunoblot analysis quantified protein expression. 15d-PGJ2 inhibited cell growth and colony formation. In addition, it reduced the expression of cyclin-dependent kinase 4 and 6 (CDK4/6) and cyclin D1 mRNA but increased p21 mRNA expression. Apoptosis was increased during cell cycle progression and induced, as evident from the expression of apoptosis-related proteins, such as reduced Bcl-2 expression and increased Bax, caspase-3, and caspase-9 expression. Furthermore, the phosphorylation of NF-κB and PI3K/AKT/mTOR proteins was suppressed. This study found that 15d-PGJ2 inhibits cell proliferation, induces apoptosis, and regulates cell cycle- and apoptosis-related gene expression by suppressing the NF-κB and PI3K/AKT/mTOR pathways in HMEC-1 cells.