Synergistic effect of metformin and medroxyprogesterone 17‑acetate on the development of endometrial cancer

Oncol Rep. 2018 Apr;39(4):2015-2021. doi: 10.3892/or.2018.6236. Epub 2018 Jan 26.


Accumulating data indicate that insulin resistance and unopposed estrogen are important risk factors of endometrial cancer (EC). Medroxyprogesterone 17‑acetate (MPA) has been used in the treatment of EC for many years. However, the therapeutic effect of this agent on EC has not been satisfactory. 36 arMetformin was recently reported to be a promising agent for the treatment of malignant diseases including EC. However, information on the synergistic effect of the two agents in EC is limited. With the aim to evaluate the synergistic effect of metformin and MPA, we conducted the present study in vitro and in vivo. We found that the combined application of metformin and MPA significantly inhibited the proliferation of the Ishikawa cells and arrested the cells in the G0/G1 phase. Furthermore, the apoptosis rate of the Ishikawa cells was significantly increased. In the animal study, the development of the xenograft tumors was significantly suppressed by the combined application of the two agents. Further investigation revealed that the synergistic inhibitory effect of the two agents on EC can be at least partly, explained by the decreased expression of cyclin D1 and cyclin E. The results of the current study provide novel insights into the treatment of EC.

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Cyclin E / genetics
  • Drug Synergism*
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Medroxyprogesterone Acetate / pharmacology*
  • Metformin / pharmacology*


  • Cyclin E
  • Cyclin D1
  • Metformin
  • Medroxyprogesterone Acetate