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Fertil Steril. 2014 May;101(5):1441-9. doi: 10.1016/j.fertnstert.2014.01.017. Epub 2014 Feb 15.

Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth.

Author information

1
Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
2
Department of Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
3
Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois. Electronic address: Sbulun@nmh.org.

Abstract

OBJECTIVE:

To assess the effect of three WNT/β-catenin pathway inhibitors-inhibitor of β-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, β-catenin levels, and cellular localization.

RESULT(S):

Inhibitor of β-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/β-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.

KEYWORDS:

Leiomyoma; WNT/β-catenin; XAV939; niclosamide; tumor biology

PMID:
24534281
PMCID:
PMC4008647
DOI:
10.1016/j.fertnstert.2014.01.017
[Indexed for MEDLINE]
Free PMC Article
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