Autophagy Attenuates Tnf-Alpha-Induced Proliferation Inhibition In The A375 Melanoma Cell Line

Objective: Autophagy plays multiple context-dependent roles in melanomagenesis and treatment resistance, and it has recently been reported that autophagy may be regulated by TNF-alpha, an important immunoinflammatory cytokine that mediates cell proliferation, differentiation and death. However, the role and mechanism of TNF-alpha in autophagy remainunclear. In this study we investigated the role and mechanism of TNF-alpha in autophagy in A375 cells. Methods: CCK-8 assays, colony formation assays and Cell-IQ Alive Image Monitoring System were used to investigate the viability, proliferation and migration of A375 cells induced by TNF-alpha, and Western blotting was used to explore the involvement of the main signals in this process; JNK, p38, ERK and P65. We used western blotting to detecte the expression of autophagy-associated proteins that induced by TNF-alpha. Results: TNF-alpha inhibited cell proliferation but not migration in A375 cells, and this effect was mediated by the p38/NF-kappa B signaling pathway. The expression of autophagy-associated proteins in cells treated with TNF-alpha was down-regulated compared to the control groups, and p38 activation was significantly up-regulated during this process. After all these studies, we showed the protective role of autophagy in TNF-alpha-induced proliferation inhibition in the A375 melanoma cell line. Conclusion: These data show that TNF-alpha-induced proliferation inhibition in the A375 melanoma cell line, and autophagy plays a protective role in this process.