Mifepristone inhibits IGF-1 signaling pathway in the treatment of uterine leiomyomas
Received 13 April 2019
Accepted for publication 7 August 2019
Published 3 September 2019 Volume 2019:13 Pages 3161—3170
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Tuo Deng
Qi Shen1, Shuangwei Zou1, Bo Sheng1, Menghuang Zhao1, Lu-Zhe Sun2, Xueqiong Zhu1
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Correspondence: Lu-Zhe Sun
Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, People’s Republic of China
Tel +86 5 778 800 2796
Fax +86 5 778 800 2560
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
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