Mifepristone inhibits IGF-1 signaling pathway in the treatment of uterine leiomyomas

Abstract

Purpose

To investigate the role of IGF-1 signaling pathway in the treatment of uterine leiomyomas with mifepristone.

Patients and methods

From October 2015 to December 2018, 50 patients with uterine leiomyoma were included in this study. Overexpression or siRNA of IGF-1 in primary human uterine leiomyoma cells were treated with or without mifepristone. MTT was used to evaluate cell viability in assays of cell proliferation and cytotoxicity. IGF-1 expression in the cells was measured with real-time RT-PCR and Western blotting and manipulated with lentivirus ectopic overexpression or siRNA silencing.

Results

Inhibition of cell viability by mifepristone was found dependent on drug concentration and treatment time. IGF-1 and phosphorylation-ERK1/2 expression were decreased, while phosphorylation-AKT expression was increased after mifepristone treatment. IGF-1 significantly promoted cell growth, while IGF-1 knockdown and mifepristone showed synergistic inhibition effects on cell growth. The overexpression of IGF-1 reversed the inhibition of cell growth and ERK1/2 phosphorylation but showed no effect on AKT phosphorylation.

Conclusion

Our study for the first time demonstrated that IGF-1 signaling via ERK1/2 appears to be an important target of mifepristone in the treatment of uterine leiomyomas, which may provide a new approach to avoid leiomyoma re-growth after cessation of mifepristone.

Keywords:

• uterine leiomyomas
• mifepristone
• IGF-1
• signal pathway

Acknowledgments

This work was supported by grants from Zhejiang Province Program for Medical and Health General Research (2015KYB251) and Wenzhou Municipal Science and Technology Bureau (Y20140697). The protocol and identification method of the immortalized human uterine leiomyoma cell line were kindly provided by Dr. Ayman Al-Hendy’s Lab.

Disclosure

The authors report no conflicts of interest in this work.