褪黑素对肺癌A549细胞诱导的血管内皮细胞增殖的影响

目的探讨褪黑素在体外共培养条件下对肺腺癌A549细胞诱导血管内皮细胞增殖的影响及相关机制。方法建立肺腺癌A549细胞和人脐静脉内皮细胞（HUVECS）ECV-304共培养模型，实验共分成四组：Con组(对照组)，nM组(褪黑素终浓度1 nM/L)，μM组(褪黑素终浓度1 μM/L)，mM组(褪黑素终浓度1 mM/L)。采用BrdU法观察不同浓度褪黑素对血管内皮细胞（ECV-304）增殖的影响，细胞迁移实验观察褪黑素对血管内皮细胞活力的抑制作用，ELISA法检测褪黑素对肺腺癌细胞VEGF蛋白表达的影响。结果低浓度的MLT(1 nM/L)对HUVECs增殖无明显影响，但高浓度 MLT(1 mM/L)明显抑制HUVECs增殖，并有浓度依赖倾向; 高浓度的褪黑素明显降低肺腺癌A549细胞培养液中VEGF的表达。 结论高浓度的褪黑素可以抑制肺腺癌细胞诱导的血管内皮细胞的增殖及迁移，其作用机制可能与褪黑素抑制肺腺癌细胞VEGF的表达有关。

Effects of Melatonin on Endothelial Cell Proliferation Induced by Lung Cancer Cell

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.