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帕立骨化醇,一种维生素 D 受体激动剂,可抑制子宫肌瘤小鼠模型中的肿瘤形成。

Paricalcitol, a vitamin d receptor activator, inhibits tumor formation in a murine model of uterine fibroids.

机构信息

Department of Obstetrics and Gynecology, Georgia Regents University, Medical College of Georgia, Augusta, GA, USA.

Center for Women's Health Research, Meharry Medical College, Nashville, TN, USA.

出版信息

Reprod Sci. 2014 Sep;21(9):1108-19. doi: 10.1177/1933719114537721. Epub 2014 Jun 12.

Abstract

We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. We found that paricalcitol has potential to reduce the proliferation of the immortalized human uterine fibroid cells. For the in vivo study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude mice supplemented with estrogen pellets. These mice were administered with vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500 ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid tumor size, the shrinkage was slightly higher in the paricalcitol-treated group. Together, our results suggest that paricalcitol may be a potential candidate for effective, safe, and noninvasive medical treatment option for uterine fibroids.

摘要

我们使用适当的子宫肌瘤细胞和动物模型进行体外和体内评估,研究了 paricalcitol(一种具有较低钙活性的 1,25-二羟维生素 D3 类似物)对子宫肌瘤的抗肿瘤和治疗潜力。我们发现 paricalcitol 具有减少永生化人子宫肌瘤细胞增殖的潜力。在体内研究中,我们通过向缺乏胸腺的裸鼠中注射 Eker 大鼠来源的子宫肌瘤细胞系 (ELT-3) 大鼠子宫肌瘤源性细胞系,并补充雌激素丸,生成皮下肿瘤。这些小鼠接受 vehicle 对照剂与 paricalcitol(300ng/kg/d)或 1,25-二羟维生素 D3(500ng/kg/d)连续 4 周的治疗,并分析数据。我们发现,虽然 paricalcitol 和 1,25-二羟维生素 D3 均显著降低了肌瘤肿瘤的大小,但 paricalcitol 治疗组的缩小幅度略高。总之,我们的结果表明,paricalcitol 可能是一种有效的、安全的、非侵入性的子宫肌瘤治疗选择的潜在候选药物。

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