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

Cai,Limin; Liu,Jing; Wang,Yu; Chen,Hongxiao; Ma,Yanli; Wang,Yanhua; Wang,Yongchen

doi:10.3892/ol.2018.8534

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

Authors:
- Limin Cai
- Jing Liu
- Yu Wang
- Hongxiao Chen
- Yanli Ma
- Yanhua Wang
- Yongchen Wang
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Affiliations: Department of Dermatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Dermatology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: April 18, 2018 https://doi.org/10.3892/ol.2018.8534
Pages: 9577-9583

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Abstract

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)‑α2b 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‑α2b. 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‑α2b response in human melanoma cells. It was determined that the overexpression of ING4 was able to increase the effects of IFN‑α2b, 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‑α2b. These findings provide a potential therapeutic strategy where a combination of ING4 overexpression and IFN‑α2b treatment may lead to higher levels of apoptosis in melanoma cells.

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