Mechanism Of Cyclooxygenase-2 Inducing Angiogenesis In Lung Adenocarcinoma By Regulating VEGF Expression

Purpose: The aim of the present study was to investigate the effect of cyclooxygenase-2(COX-2)on tumor angiogenesis by regulating vascular endothelial growth factor(VEGF)in the microenvironment of lung adenocarcinoma A549 cells.Methods: A549 cells were transfected with siRNA-COX-2(small interference RNA for COX-2 gene),siRNA-VEGF(small interference RNA for VEGF gene)or p LV-COX-2(plasmid overexpressing COX-2 gene),the tranfection rate was determined by western bloting.The expression levels of VEGF protein were measured by WB,and the expression level of VEGF in the cell supernatants was quantified by ELISA.The conditioned media were collected,human umbilical vein endothelial cells(HUVECs)were cultured with the conditioned media collected from A549 cells,and their proliferative,migratory,invasive and tube forming abilities were assessed by MTT,cell scratch assay,cell migration assay and tube formation assay,respectively.Each experiment was repeated for three times,and the results were analyzed statistically.Results: The present results showed that siRNA-COX-2 inhibited the expression levels of COX-2 and VEGF,whereas p LV-COX-2 exhibited an opposite trend.In addition,HUVEC proliferative rate,migratory rate,invasive cell number and total tube length were decreased following exposure to conditioned media collected from A549 cells transfected with siRNA-COX-2,whereas conditioned media from A549 cells transfected with p LV-COX-2 exhibited opposite effects.Moreover,VEGF knockdown in A549 cells weakened COX-2 mediated proliferative,migratory,invasive and tube forming effects in HUVECs.Conclusion: Our findings indicated that COX-2 promoted HUVEC proliferation,migration,invasion and tube formation via VEGF,suggesting that COX-2 may be involved in lung adenocarcinoma angiogenesis.COX-2/VEGF signaling pathway may be a potential therapeutic target to treat lung adenocarcinoma in the future.