Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
Department of Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
Fertil Steril. 2014 May;101(5):1441-9. doi: 10.1016/j.fertnstert.2014.01.017. Epub 2014 Feb 15.
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.
Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.
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.
评估三种 WNT/β-连环蛋白通路抑制剂（β-连环蛋白和 TCF4 的抑制剂（ICAT）、尼立达唑和 XAV939）对人子宫肌瘤细胞原代培养增殖的影响。
人子宫肌瘤细胞的前瞻性研究，来源于子宫肌瘤切除术或子宫切除术。
大学研究实验室。
年龄 27-53 岁行手术的女性（n=38）。
腺病毒 ICAT 过表达或用不同浓度的尼立达唑或 XAV939 处理。
细胞增殖、细胞死亡、WNT/-连环蛋白靶基因表达或报告基因调控、β-连环蛋白水平和细胞定位。
ICAT、尼立达唑或 XAV939 抑制β-连环蛋白和 TCF4，或抑制 WNT/β-连环蛋白通路激活，并在人子宫肌瘤细胞原代培养中发挥抗增殖作用。
三种 WNT/-连环蛋白通路抑制剂特异性阻断人子宫肌瘤生长和增殖，提示经典 WNT 通路可能是治疗子宫肌瘤的潜在治疗靶点。我们的研究结果为进一步临床前和临床评估 ICAT、尼立达唑和 XAV939 作为子宫肌瘤候选抗肿瘤药物提供了依据。
