Abstract: Objective To investigate the effects of hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor YC-1 on hypoxia induced human pulmonary artery smooth muscle cells (HPASMCs) proliferation, apoptosis and the expression of p53, and explore the molecular mechanism in the processes. Method HPASMCs were cultured in DMEM medium supplemented with 10%FBS in vitro. Then divided them into four groups: normoxia, hypoxia and hypoxia+YC-1(0.01 and 0.05mmol/L). Cells proliferation was measured by CCK-8, and the apoptosis was detected by flow cytometry. The expression of HIF-1α and p53 were tested by Western Blot, and the mRNA expression of p53 was tested by RT-PCR. Results Hypoxia can promote the proliferation of HPASMCs. Treatment of HPASMCs with different concentrations of YC-1 intervention for 24h obviously dropped proliferation rate (P<0.05), and the apoptosis rate increased significantly (P<0.05). YC-1 can also down-regulate the expression of HIF-1α and up-regulate the expression of p53 significantly (P<0.05). Conclusion YC-1 can inhibit hypoxia-induced HPASMCs proliferation and promote apoptosis, and the mechanism probably related to the up-regulation of p53 expression.

Key words: YC-1, HPASMCs, Proliferation, Apoptosis, p53