Abstract: ObjectiveTo explore the effect of melatonin on endothelial cells proliferation induced by lung cancer cells A549 using a coculture system in vitro and its mechanism. Methods Lung cancer cells were cocultured with endothelial cells(HUVECs) in transwell chamber culture system.The cells were divided randomly into four groups: C group,nM group(final concentration of melatonin in the medium,1 nM/L),μM group(final concentration of melatonin in the medium,1 μM/L) and mM group(final concentration of melatonin in the medium,1 mM/L). Brdu method was carried out to assay the proliferation of HUVECs when treated with melatonin in concentrations from 1 nmol/L to 1 mM/L(final concentration in the medium).Transwell chamber assay was applied to measure the migration of HUVECs,and ELISA assay was performed to detect the VEGF protein levels in tumor cells. ResultsAt near physiological concentrations(1nM/L),melatonin had no significant effect on cellular proliferation. However,melatonin in higher concentrations (1mM/L) significantly decreased cell proliferation,and the negative effect on HUVECs proliferation was enhanced with increasing melatonin concentrations.Pharmacologic concentrations of melatonin(1mM/L) significantly suppressed the VEGF protein levels. ConclusionHigh concentrations of melatonin markedly reduces HUVECs proliferation and migration.The protective mechanism might associate with suppression of VEGF protein expression.