Resveratrol inhibits hypoxia-induced proliferation and migration of pulmonary artery vascular smooth muscle cells by inhibiting the phosphoinositide 3-kinase/protein kinase B signaling pathway

Hypoxia is a risk factor for severe chronic obstructive pulmonary disease, which aggravates the disease and may cause mortality by inducing hypoxic pulmonary hypertension (HPH). Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) may mediate this effect. Resveratrol is a phenolic compound extracted from a plant and has been reported to alleviate HPH, although the underlying mechanisms remained to be elucidated. In cancer, resveratrol has been reported to abrogate the phosphoinositide 3-kinase/protein kinase B (AKT) signaling pathway, thereby inhibiting tumor development. Therefore, the present study aimed to investigate the role of resveratrol in preventing PASMCs from proliferating and migrating. Resveratrol was demonstrated to be inhibitory in a dose-dependent manner on hypoxia-induced cell proliferation and migration, and protein expression levels of phosphorylated AKT and AKT. Additionally, resveratrol was identified to act synergistically with LY-294002, a phosphorylation inhibitor of AKT, but antagonistically with insulin-like growth factor-1, an agonist of AKT phosphorylation. This suggested that resveratrol may reduce proliferation and migration by diminishing expression and phosphorylation of AKT, thereby preventing development of HPH.