Objective: To determine the effect of prostaglandin E2 (PGE2) on brain metastasis of lung cancer,and to explore the possible mechanism of aspirin (PGE2 inhibitor) reducing brain metastasis of lung cancer.
Methods: Radioimmunoassay was performed to measure the expression level of PGE2 in cell supernatant collected from cells treated with or without aspirin (8 mmol/L) at different time points. After establishing in vitro blood-brain barrier (BBB) model using Transwell, lung cancer cells was added to upper chamber of transwell and was then treated with aspirin (8 mmol/L). Western blot was used to examine the expression of occludin protein in brain microvascular endothelial cells. The permeability changes of BBB model in vitro were determined using horseradish peroxides. The number of lung cancer cells passing through BBB model in vitro was counted with Hemocytometer. Effect of aspirin on brain metastasis of lung cancer was observed in nude mice in the animal level.
Results: PGE2 level decreased and reached minimum level 120 min after aspirin treatment in lung cancer cells culture fluid. Occludin expression increased and reached maximum level 120 min after aspirin treatment in brain microvascular endothelial cells. At the same time,permeability of BBB and number of lung cancer cells passing through BBB also reached the lowest value 120 min after aspirin treatment. Aspirin significantly reduced the incidence of brain metastasis of lung cancer in animal model.
Conclusion: Aspirin reduced occurrences of the brain metastasis of lung cancer in animal model,which may be caused by inhibition of PGE2 released by lung cancer cells and upregulation of occludin expression therefore leading to decrease in BBB permeability.
Keywords: Aspirin; Blood-brain barrier; Brain metastasis of lung cancer; Lung cancer; Occludin protein; Prostaglandin.