Migration and invasion in B16-F10 mouse melanoma cells are regulated by Nrf2 inhibition during treatment with ionizing radiation.

Nuclear factor erythroid 2-related factor 2 (Nrf2) serves a critical role in carcinogenesis. The present study examined the effect of Nrf2 on the proliferation and invasion of melanoma cells that were treated with ionizing radiation. B16-F10 mouse melanoma cells were exposed to various doses of ionizing radiation for different time periods. Small interfering (si)RNAs targeting Nrf2 were transfected into B16-F10 cells, and cell proliferation, invasion and apoptosis were detected by Transwell, MTT or western blot assays. The expression of Nrf2 and its downstream heme oxygenase 1 (HO-1) was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. HO-1 activity was also examined. Ionizing radiation stimulated Nrf2 expression, increased caspase-3 expression, and reduced the viability, migration and invasion of B16-F10 mouse melanoma cells. Transfection with Nrf2 siRNA was able to inhibit Nrf2 and HO-1 expression in B16-F10 mouse melanoma cells that were treated by ionizing radiation. Inhibition of Nrf2 further reduced cell viability, invasion and migration, and elevated caspase-3 expression in B16-F10 mice melanoma cells that were treated by ionizing radiation. In summary, treatment with ionizing radiation was able to stimulate Nrf2 expression and regulate cell viability, invasion and migration of B16-F10 cells. A combination of Nrf2 knockdown and ionizing radiation treatment exerted a synergistic effect on migration, invasion and apoptosis in B16-F10 murine melanoma cells.