Ulipristal acetate induces cell cycle delay and remodeling of extracellular matrix

Shin,So‑Jin; Kim,Jinyoung; Lee,Seungmee; Baek,Jongwoo; Lee,Jin  Eui; Cho,Chiheum; Ha,Eunyoung

doi:10.3892/ijmm.2018.3779

Ulipristal acetate induces cell cycle delay and remodeling of extracellular matrix

Authors:
- So‑Jin Shin
- Jinyoung Kim
- Seungmee Lee
- Jongwoo Baek
- Jin Eui Lee
- Chiheum Cho
- Eunyoung Ha
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Affiliations: Department of Gynecology and Obstetrics and Institute for Cancer Research, School of Medicine, Keimyung University, Daegu, North Gyeongsang 42403, Republic of Korea, Department of Internal Medicine, School of Medicine, Keimyung University, Daegu, North Gyeongsang 42403, Republic of Korea, Department of Obstetrics and Gynecology, Gumi CHA Hospital, CHA University, Gumi, North Gyeongsang 39295, Republic of Korea, Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA, Department of Biochemistry, School of Medicine, Keimyung University, Daegu, North Gyeongsang 42403, Republic of Korea
Published online on: July 17, 2018 https://doi.org/10.3892/ijmm.2018.3779
Pages: 1857-1864
Copyright: © Shin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uterine leiomyoma is a benign tumor that grows within the muscle tissue of the uterus. Ulipristal acetate (UPA) is a pre‑operative drug used to reduce the size of leiomyoma. The aim of the present study was to examine the in vitro mechanistic details of action of UPA on uterine leiomyomas. Primary cultures of leiomyoma cells were isolated from patient myomectomy specimens and incubated in the presence or absence of UPA at various concentrations. The proliferation, cell viability and doubling time properties of the treated cells were analyzed. In addition, the mRNA and protein expression levels of p21, p27, cyclin E, cyclin‑dependent kinase 2 (CDK2), matrix metalloproteinase (MMP)‑2 and MMP‑9 were examined, as well as the structure of F‑actin in the primary‑cultured leiomyoma cells. The results demonstrated that UPA exerted inhibitory effects on proliferation of primary‑cultured leiomyoma cells. Expression of p21 and p27 was upregulated, while cyclin E and CDK2 were downregulated in UPA‑treated primary‑cultured leiomyoma cells. An increased expression of MMP‑2 was observed in primary‑cultured leiomyoma cells and a leiomyoma tissue sample of a patient with previous history of UPA treatment. Furthermore, a pronounced formation of F‑actin stress fibers was observed in leiomyoma cells of the UPA‑treated patient. These data suggest that UPA treatment attenuated the proliferation of uterine fibroid cells via upregulation of p21 and p27, resulting in cell cycle delay. The findings in the current study also suggest that UPA may cause extracellular matrix constriction, leading to the shrinkage in size of the leiomyoma possibly via stimulation of MMP‑2 expression and induction of actin stress fibers.

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