醋酸乌利司他 (UPA) 是一种选择性黄体酮受体调节剂，用于治疗子宫肌瘤（一种良性肿瘤）。子宫肉瘤是一种恶性程度很高的癌症，临床上与子宫肌瘤相似，预后较差。目前尚无UPA对子宫肉瘤作用的实验研究。在这项研究中，我们通过体外和体内动物模型检查了 UPA 对子宫肉瘤的疗效。 UPA 的细胞毒性在子宫肉瘤细胞系（MES-SA、SK-UT-1 和 SK-LMS-1）中测定。分别通过子宫肉瘤细胞系的互补 DNA (cDNA) 微阵列和蛋白质印迹分析受 UPA 影响的凋亡基因和信号通路。使用子宫肉瘤细胞系和患者来源的异种移植 (PDX) 小鼠模型检查了 UPA 的体内功效。 UPA 抑制子宫肉瘤细胞系和 PDX 小鼠 (PDX-C) 的原代培养细胞的细胞生长。 cDNA 微阵列分析显示 CCL2 被 UPA 高度下调。 UPA 抑制 STAT3 的磷酸化和总表达。 UPA 还抑制 PDX-C 中的 CCL2 和 STAT3。 UPA的抑制作用在PR过表达和黄体酮治疗中没有改变。对细胞系来源的异种移植物和平滑肌肉瘤（一种典型的子宫肉瘤）的 PDX 模型进行的体内疗效研究表明，UPA 显着降低了肿瘤生长。 UPA 通过抑制 STAT3/CCL2 信号通路对子宫肉瘤具有显着的抗肿瘤作用，可能成为治疗该疾病的潜在治疗剂。版权所有 © 2023 作者。由 Elsevier Masson SAS 出版。保留所有权利。

Ulipristal acetate (UPA) is a selective progesterone receptor modulator and is used for the treatment of uterine leiomyoma (a benign tumor). Uterine sarcoma which is highly malignant cancer with a poor prognosis is clinically resembled with uterine leiomyoma. There has been no experimental research on the effect of UPA on uterine sarcoma. In this study, we examined the efficacy of UPA in uterine sarcoma with in vitro and in vivo animal models. Cytotoxicity of UPA was determined in uterine sarcoma cell lines (MES-SA, SK-UT-1, and SK-LMS-1). Apoptotic genes and signaling pathways affected by UPA were analyzed by complementary DNA (cDNA) microarray of uterine sarcoma cell lines and western blot, respectively. An in vivo efficacy of UPA was examined with uterine sarcoma cell line- and patient-derived xenograft (PDX) mice models. UPA inhibited cell growth in uterine sarcoma cell lines and primary culture cells from a PDX mouse (PDX-C). cDNA microarray analysis revealed that CCL2 was highly down-regulated by UPA. Phosphorylation and the total expression of STAT3 were inhibited by UPA. UPA also inhibited CCL2 and STAT3 in PDX-C. The inhibitory effect of UPA had not changed in the overexpression of PR and treatment of progesterone. In vivo efficacy studies with cell line-derived xenografts and a PDX model with leiomyosarcoma, a typical uterine sarcoma, demonstrated that UPA significantly decreased tumor growth. UPA had significant anti-tumor effects in uterine sarcoma through the inhibition of STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.