Antitumor activity of interleukin-18 on A549 human lung cancer cell line

OBJECTIVE: In this study, we investigated the antitumor activity of interleukin (IL)-18 on A549 human lung cancer cell line and evaluated the potential of IL-18 therapy in lung cancer. MATERIALS AND METHODS: We generated a human IL-18 lentiviral expression vector and examined three groups of A549 cells, including nontransduced cells and cells transduced with either IL-18 or an empty lentiviral expression vector. IL-18 expression, cell proliferation, and apoptosis were examined using Western blotting, methylthiazolyldiphenyl-tetrazolium bromide assay, and flow cytometry, respectively. The expression of the T helper 1 (Th1) cytokine interferon-γ (IFN-γ) and Th2 cytokine IL-4 was analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to the other groups of cells, A549 cells transduced with the IL-18 lentiviral expression vector exhibited significant increases in IL-18 expression, apoptosis, and the fraction of cells in G0 and G1 phases of the cell cycle and significant decrease in proliferation. Furthermore, ELISA results showed that IFN-γ expression increased significantly and IL-4 decreased in A549 cells transfected with IL-18 lentivirus expression vector. CONCLUSION: Using a lentiviral expression vector, IL-18 was expressed stably and efficiently in A549 cells, which showed attenuated proliferation and tumor cell growth, and enhanced tumor cell apoptosis. IL-18 expression also induced the secretion of IFN-γ, while decreasing the production of IL-4, therefore restoring the balance between Th1/Th2 cell subsets. These findings further demonstrated the antitumor activity of IL-18 and might open new therapeutic avenues for the prevention and treatment of lung cancer.