Objective: To investigate the effect of mitogen-activated protein kinase (MAPK) signal cascade in the non-estrogen antagonistic mechanism of tamoxifen (TAM).
Methods: Human breast cancer cells MCF-7 were cultured. TAM, PD98075, inhibitor of MAPK kinase (MEK), or TAM + PD98075 was added into the culture media, followed by methyl thiazolyl tetrazolium (MTT) and DMSO. Then the 542nm absorption value was measured and the growth curve was drawn. Western blot was used to measure the expression of p-extracellular signal-regulated kinase (ERK) in MCF-7 cells. Flow cytometry was applied to analyze the cell cycle and apoptosis.
Results: The optical density representing the relative expression of p-ERK was lower successively in the control, TAM, PD09875, and TAM + PD09875 groups. The apoptotic rate of MCF-7 cells was 6.44%, 8.3%, 36.5% and 53.5% in the control, PD98075, TAM, and TAM + PG98075 groups respectively The rate of cells in G(0)G(1) phase was 74.25%, 79.76%, 84.02%, and 95.82% in those groups respectively. Ther rate o cells in S phase was 21.03%, 15.22%, 11.43%, and 2.22% respectively in those groups. The rate of cells in G(2)M phase was 4.71%, 5.02%, 4.52%, and 1.96% respectively in those groups.
Conclusion: MAPK signal transduction pathway plays a certain role in the non-estrogen antagonistic mechanism of tamoxifen.