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Expression of NR1H3 in endometrial carcinoma and its effect on the proliferation of Ishikawa cells in vitro

Authors Fang F, Li D, Zhao L, Li Y, Zhang T, Cui B

Received 17 July 2018

Accepted for publication 5 November 2018

Published 18 January 2019 Volume 2019:12 Pages 685—697


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava

Fang Fang,1,2 Dawei Li,1,2 Lu Zhao,1 Yue Li,1,2 Teng Zhang,1 Baoxia Cui1

1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Obstetrics and Gynecology, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China

Purpose: Our study aimed to investigate the expression of NR1H3 in endometrial carcinoma, its effect on the proliferation of endometrial carcinoma cells in vitro, and the underlying mechanism of this effect.
Materials and methods: Immunohistochemistry of paraffin-embedded, sectioned specimens and of a tissue microarray was conducted to estimate the expression of NR1H3 (liver X receptors α: LXRα) and NR1H2 (liver X receptors β: LXRβ) in endometrial carcinoma tissues. The subcellular localization of NR1H3 in the endometrial carcinoma cell line Ishikawa was determined by immunofluorescence. An agonist of NR1H3, TO901317, was then administered to activate the expression of NR1H3, and cell viability and cell-cycle progression were investigated through MTT and flow cytometric assays, respectively. The gene and protein expression levels of NR1H3, cyclin D1 (CCND1), and cyclin E (CCNE) in cells pretreated with different concentrations of TO901317 for different periods of time were also detected by real-time RT-PCR and Western blot, respectively.
Results: The results showed that, in contrast to NR1H2, which was expressed at low levels in endometrial tissues, NR1H3 was upregulated in endometrial adenocarcinoma tissues compared to levels in normal endometrial tissues and endometrial polyps. Moreover, NR1H3 was mainly expressed in the cytoplasm of Ishikawa cells. TO901317 significantly decreased cell viability and arrested the cell cycle in Ishikawa cells in a dose- and time-dependent manner. Furthermore, the administration of TO901317 not only promoted the expression of NR1H3 but also inhibited the expression of CCND1 and CCNE in Ishikawa cells.
Conclusion: We demonstrated that NR1H3 is upregulated in endometrial adenocarcinoma and that it inhibits cell viability by inhibiting the expression of CCND1 and CCNE in endometrial carcinoma cells. Our study indicates that NR1H3 may play a role in the development of endometrial cancer and may emerge as a promising therapeutic target.

Keywords: liver X receptor, CCND1, endometrial carcinoma, cell proliferation, cell cycle

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