Effects of NEDD8 covalent modification inhibitor MLN4924 on proliferation and apoptosis of human ovarian cancer cell line SKOV3 / 中国免疫学杂志

ABSTRACT

Objective:To explore the effects of neural precursor cell-expressed developmentally down regulated 8(NEDD8) covalent modification on ovarian cancer cell proliferation and apoptosis,and the possible underlying mechanisms.Methods:Use different concentrations of MLN4924 (0,0.125,0.25,0.5 mol/L) and human ovarian cancer cell line SKOV3,the expression levels of PAR3, HER2,Neddylated-cullins,P-IκBα were detected by Western blot and the secretion of IL-6 was measured by ELISA after 4 h treatment.The cell proliferation was determined by CCK-8 staining and the cell cycle and apoptosis were analyzed by flow cytometry after 72 h treatment.Results:MLN4924 inhibits the proliferation of SKOV3 cells in a dose-dependent manner,which is associated with reduced IL-6 secretion.Western blot revealed that MLN4924 dose-dependently inhibits the neddylation of cullins(reduced neddylated-cullins) and induced the accumulation of P-IκBα,whereas the expression levels of PARs and HER2 remained largely unchanged.At the same time MLN4924 dose-dependently induced cell cycle prove at S phase and the formation of a large number of tetraploids.Furthermore,apoptosis increased with the dose of MLN4924.Conclusion:NEDD8 covalent modification specific inhibitor MLN4924 can significantly inhibit the proliferation of SKOV3 cells and induce cell cycle arrest and apoptosis.The above inhibitory effects may partially result from impaired P-IκBα degradation and IL-6 secretion.