Effects of NEDD8 covalent modification inhibitor MLN4924 on proliferation and apoptosis of human ovarian cancer cell line SKOV3
10.3969/j.issn.1000-484X.2018.03.005
- VernacularTitle:NEDD8共价修饰抑制因子MLN4924对人卵巢癌细胞株SKOV3增殖和凋亡的影响
- Author:
Jian LIU
1
;
Hui-Fang WU
;
Ya-Wei ZHAO
;
Ji-Yan ZHANG
Author Information
1. 广西医科大学,南宁530021
- Keywords:
MLN4924;
Ovarian cancer cell;
Cell proliferation;
Cell apoptosis;
IL-6
- From:
Chinese Journal of Immunology
2018;34(3):340-343,348
- CountryChina
- Language:Chinese
-
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.
