Enhanced anti-melanoma efficacy of interferon alpha-2b via overexpression of ING4 by enhanced Fas/FasL-mediated apoptosis

摘要

Melanoma, is a highly aggressive and the most lethal form of skin cancer, and is known to be resistant to current therapeutic modalities. Interferon (IFN)-alpha 2b is an immunostimulatory cytokine and is used to treat melanoma by inhibiting proliferation and promoting apoptosis of cells. However, there is a need to improve the efficacy of IFN-alpha 2b. Inhibitor of growth family member 4 (ING4) has been reported to function as a tumor suppressor and is involved in regulating cell cycle progression, apoptosis, cell migration and invasion. Previously studies have also reported that caspase-3, caspase-8, poly (ADP-ribose) polymerase (PARP) and Fas/Fas ligand (FasL) pathways are involved in the process of apoptosis. In the present study, it was investigated whether overexpression of ING4 is able to enhance IFN-alpha 2b response in human melanoma cells. It was determined that the overexpression of ING4 was able to increase the effects of IFN-alpha 2b, and induce cell death and apoptosis in melanoma cells. Furthermore, the overexpression of ING4 resulted in decreased expression of PARP, caspase-3 and -8. The expression of cleaved PARP, cleaved caspase-3, cleaved caspase-8, Fas and FasL was increased in the A375 melanoma cell line. These results demonstrate that the overexpression of ING4 is able to enhance the anti-melanoma activity of IFN-alpha 2b. These findings provide a potential therapeutic strategy where a combination of ING4 overexpression and IFN-alpha 2b treatment may lead to higher levels of apoptosis in melanoma cells.