Effect of different concentrations of medroxyprogesterone acetate combined with 17β-estradiol on endothelial progenitor cells

OBJECTIVE: Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelial cells. Inhibition of EPC proliferation and migration may be a new method for anti-tumor therapy. Medroxyprogesterone acetate (MPA) may act on tumor angiogenesis by impacting biological functions of EPCs. The aim of this work was to study the effect of different concentrations of MPA combined with 17 beta-estradiol (17 beta-E2) on proliferation, migration, and apoptosis of EPCs in vitro. MATERIALS AND METHODS: Proliferation tests (MTT analysis) and migration assay of EPCs, isolated from bone marrow of canine, were performed to detect their response to different concentrations of MPA combined with 17 beta-E2 (1 x 10(-8) mol/L). The growth curves were drawn every 24 h for 7 consecutive days. The cell cycle and apoptosis of EPCs were analyzed by flow cytometry. RESULTS: 17 beta-E2 (1 x 10-8 mol/L) increased EPC proliferation, while lower concentration of MPA (<= 10(-5) mol/L) partially inhibited it. The higher concentration of MPA (<= 10(-4) mol/L) combined with 17 beta-E2 had a significant inhibitory effect on EPC growth, arresting it in the S phase. It also increased the apoptosis rate and damaged the migration ability of EPCs. CONCLUSIONS: Low concentration of MPA partially inhibited the function of 17 beta-E2 that promotes the proliferation of EPCs. However, high concentration of MPA combined with 17 beta-E2 inhibited a variety of biological functions of EPCs. So, the MPA has a bidirectional effect combined with 17 beta-E2 on the cell biology of EPCs.