Aim: Interleukin-33 (IL-33), belonging to IL-1 family cytokines, has been reported to participate in cancer growth and metastasis. The clinical values of IL-33 in lung cancer have been previously investigated. We aimed to elucidate the probable role of IL-33 in the migration and invasion of lung cancer cells.
Methods: Cell migration and invasiveness were tested by Transwell assay. Western blotting analysis was performed to detect protein expression.
Results: We found that IL-33 treatment in human lung A549 cells dose-dependently enhanced their migratory and invasive ability, accompanied by elevated expression of matrix metalloproteinase (MMP) 2 and MMP9. Meanwhile, IL-33-induced cell migration and invasion were significantly abolished by small interfering RNA-targeting ST2, the specific receptor of IL-33. Furthermore, IL-33 exposure induced the phosphorylation of AKT. Pretreatment with an AKT inhibitor LY294002 markedly attenuated IL-33-induced cell migration and invasion.
Conclusion: IL-33/ST2 promoted the migration and invasiveness of lung cancer cells through AKT pathway. Our findings strongly suggest that IL-33 may serve as a promising therapeutic strategy for lung cancer.
Keywords: ST2, AKT, migration, invasion