Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth

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• 作者：Masanori Ono ; M.D. ; Ph.D.^a ; Ping Yin ; Ph.D.^a ; Antonia Navarro ; M.Sc.^a ; Molly B. Moravek ; M.D.^a ; John S. Coon V ; M.Sc.^a ; Stacy A. Druschitz ; B.Sc.^a ; Cara J. Gottardi ; Ph.D.^b ; Serdar E. Bulun ; M.D.^a ; ^{Sbulun@nmh.org" class="auth_mail}
• 关键词：Leiomyoma ; WNT/尾-catenin ; niclosamide ; XAV939 ; tumor biology
• 刊名：Fertility and Sterility
• 出版年：May 2014
• 年：2014
• 卷：101
• 期：5
• 页码：1441-1449.e1
• 全文大小：1135 K

文摘

To assess the effect of three WNT/尾-catenin pathway inhibitors—inhibitor of 尾-catenin and TCF4 (ICAT), niclosamide, and XAV939—on the proliferation of primary cultures of human uterine leiomyoma cells.

Design

Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.

Setting

University research laboratory.

Patient(s)

Women (n = 38) aged 27–53 years undergoing surgery.

Intervention(s)

Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939.

Main Outcome Measure(s)

Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, 尾-catenin levels, and cellular localization.

Result(s)

Inhibitor of 尾-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/尾-catenin pathway activation and exert antiproliferative effects in primary cultures of human leiomyoma cells.

Conclusion(s)

Three WNT/-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate antitumor agents for uterine leiomyoma.