Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells

摘要

BACKGROUND AND AIMS: Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. However, the mechanisms are not very clear. In this study, we investigated the effects of propofol on the proliferation, invasion and angiogenesis of human Eca-109 cells, and explored the mechanism. METHODS: The human Eca-109 cells was treated with propofol at the concentrations of 10-100 μmol/L for 72 hours or at the concentration of 100 μmol for 8-72 hours. Cell viability was determined by the MTT assay; the effect of propofol on apoptosis by 5′-triphosphate-biotin nick end labeling (TUNEL) staining. The effect of propofol on angiogenesis was determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The effect of propofol on cell invasion using a modified Matrigel Boyden chamber assay. ERK1/2, MMP-9 and VEGF leves was detected by western blotting assay. RESULTS: In human Eca-109 cells, propofol significantly promoted cell apoptosis and inhibited proliferation in a dose and time-dependent manner. Furthermore, propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol significantly dose and time-dependently down-regulated gene expression and protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP-9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9 signaling pathways. It was noteworthy that the ERK activator (phorbol 12-myristate 13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after propofol treatment, and led to significant increase of proliferation, invasion and angiogenesis. CONCLUSIONS: These findings indicate that propofol inhibited proliferation, invasion and angiogenesis of human Eca-109 cells in vitro through modulation of ERK-VEGF /MMP-9 signaling. Propofol not only can be an anesthesia agent which reduces pain but plays an important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.