Inhibition of proliferation of breast cancer cells by down-regulation of cyclin d1 and survivin protein expression by erk inhibitor u0126 / 中国药理学通报

ABSTRACT

AimTo investigate the inhibitory effect of ERK signaling pathway inhibitor UO126 on breast cancer cell proliferation and explore its specific regulatory mechanism. Methods Cultured human breast cancer cell MCF-7, MDA-MB231, the cell were divided into different groups and intervened. MTT was used to measure the cell proliferation; Flow cytometry was employed to test cell cycle and cell apoptosis; Western blot was applied to test p-ERK/ERK, cyclin D1, survivin and cleaved caspase-3 protein expression. Results The results of MTT showed that the inhibitory rate of MCF-7 and MDA-MB231 cells increased significantly after U0126 intervention for 24 h and 48 h(P < 0.01). Cell cycle and apoptosis were detected by MCF-7 and MDA-MB231 cells treated with U0126 for 24 h. The proportion of cells in G0/G1 phase was significantly higher than that in control group, and the proportion of cells in S and G2 phase decreased(P < 0.05). The apoptotic rate in intervention group was significantly higher than that in non-intervention group, and the difference was significant(P < 0.01); U0126 treatment of human breast cancer cells could block ERK phosphorylation, increase cyclin D1 protein expression, inhibit survivin and up-regulate cleaved caspase3 expression, which were significantly different from control group(P < 0.05). Conclusions U0126 blocks ERK signaling pathway in MCF-7, MDA-MB231, down-regulates the cyclin D1, and blocks cell cycle in G0/G1 phase, then it inhibits the expression of survivin and increases cleaved caspase-3, promotes cell apoptosis, and inhibits the proliferation of breast cancer cell MCF-7, MDA-MB231.