关键词: 三氧化二砷;A375细胞;凋亡, NF-κB;C-IAP2;Caspase-3

Abstract: BACKGROUND AND AIM: To explore the effects on the variation of nuclear factor kappa B (NF-κB), C-IAP2 and Caspase-3 during apoptosis of human melanoma A375 cells induced by arsenic trioxide. MATERIALS AND METHODS: A375 cells were treated with arsenic trioxide alone or together with Ac-devd-cho (N-Acetyl-Asp-Glu-Val-Asp-CHO). The expression of NF-κB p65 nuclear protein and the activity of Caspase-3 were examined by Western blot, the cleaved Caspase-3 was detected by immunohistochemistry, the expression of C-IAP2 mRNA was examined by semi-quantitative RT-PCR. RESULTS: Treated with 5.0 μmol/L As2O3 alone for 12 and 24 hours; co-treatment with 5.0 μmol/L As2O3 and 20 μmol/L Ac-devd-cho for 24 hours; with increasing concentration of As2O3 , Caspase-3 was activated dramatically, NF-κB p65 and C-IAP2 mRNA expressions were decreased dramatically. Immunohistochemistry demonstrated that the cleaved Caspase-3 protein advanced in parallel with As2O3 concentration increase and response time extension, but could be partly blocked by Ac-devd-cho. CONCLUSION: As2O3 could induce the apoptosis of A375 cells and could be partially blocked by Ac-devd-cho. With the concentration increased and response time extension, the Caspase-3 protein was activated markedly,but blocked by Ac-devd-cho. NF-κB and C-IAP2 were suppressed, and could not be blocked by Ac-devd-cho. The signal transduction pathways of NF-κB, C-IAP2 and Caspase-3 might be associated with the apoptosis of A375 cells induced by As2O3.

Key words: As2O3, A375 cells, apoptosis, NF-κB, C-IAP2, Caspase-3