Mobile website
Archive > Volume 22 Issue 4 > 2015,22(4):438-442. DOI:10.3872/j.issn.1007-385X.2015.04.005 Prev Next
Basic Research
4EGI-1 induced AKT activation counteracts its growth inhibition on A375 cell
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective:To investigate the effect of 4EGI-1 on AKT activity in melanoma cell A375 and its role in 4EGI-1-induced growth inhibition of the cells. Methods: After treated with indicated concentrations of 4EGI-1（20, 40, 60 μmol/L）for 12 h, A375 cells were lysed to analyze AKT phosphorylation by using immunoblotting. A375 cells were also treated with 4EGI-1 and BEZ235 alone or in combination to assess their effects on cell proliferation through the CCK-8 assay. Their influences on cell cycle were determined using flow cytometry and the expression of Cyclin D1 was examined by immunoblotting.Results: 4EGI-1 induced AKT phosphorylation in A375 cells dose-dependently. While the inhibition rates of 4EGI-1 and BEZ235 on A375 cells were (7.6±1.2)% and (2.4±3.1)% respectively, the rate increased significantly to (19.8±4.3)% when both compounds were used together. The percentage of cells in S phase cells were 2565% and 25.82% after treated with 4EGI-1 or BEZ235. It decreased to 13.08% in A375 cells exposed to both 4EGI-1 and BEZ235, indicating that BEZ235 enhanced the inhibitory effect of 4EGI-1 on A375 growth. BEZ235 also enhanced the inhibitory effect of 4EGI-1 on cyclin D1 expression. The relative expression levels of cyclin D1 in 4EGI-1 group and BEZ235 group were 0.81±0.04 and 0.04±0.76 respectively, it was reduced to 0.25±0.03 when the cells were cultured in the presence of both compounds. Conclusion: Akt phosphorylation induced by 4EGI-1 counteracts its growth inhibition on A375 cell. Combination of 4EGI-1 and Akt inhibitor is a more effective strategy to inhibit the growth of A375 cells.
Keywords:
Project Supported:
Project supported by the Modernization of Traditional Chinese Medicine Special Project of Guizhou Province（No. 20125018）
Clc Number:
