Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth.
Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth.
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DOI：
10.1016/j.fertnstert.2014.01.017
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发表时间：
2014-05
影响因子：
6.7
通讯作者：
Bulun SE
中科院分区：
文献类型：
--
作者：
Ono M;Yin P;Navarro A;Moravek MB;Coon V JS;Druschitz SA;Gottardi CJ;Bulun SE
评估三种WNT/β-catenin通路调节剂-β-catenin和TCF 4的抑制剂（ICAT）、氯硝柳胺和XAV 939-对人子宫平滑肌瘤细胞原代培养物增殖的影响。从子宫肌瘤切除术或子宫切除术中获得的人平滑肌瘤细胞的前瞻性研究。大学研究实验室。接受手术的27-53岁女性（n = 38）。腺病毒ICAT过表达或用不同浓度的氯硝柳胺或XAV 939处理。细胞增殖、细胞死亡、WNT/β-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。β-连环蛋白和TCF 4的抑制剂、氯硝柳胺或XAV 939抑制WNT/β-连环蛋白通路活化，并在人平滑肌瘤细胞的原代培养物中发挥抗增殖作用。三种WNT/β-catenin通路抑制剂特异性阻断人子宫肌瘤的生长和增殖，表明经典的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ICAT、氯硝柳胺和XAV 939作为子宫肌瘤候选抗肿瘤药物的进一步临床前和临床评价提供了依据。
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. Women (n = 38) aged 27–53 years undergoing surgery. Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939. Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, β-catenin levels, and cellular localization. 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. 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.