Yang Yang, Li Xin, Mamouni Kenza, Kucuk Omer, Wu Daqing
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Georgia Cancer Center and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, U.S.A.
Anticancer Res. 2017 Nov;37(11):6235-6243. doi: 10.21873/anticanres.12074.
Mifepristone has gained great interest in its potential as a novel agent against human cancers, including prostate cancer (PCa). However, recent clinical trials using mifepristone in PCa and other cancers have been disappointing. We evaluated the in vitro and in vivo activities of mifepristone, in combination with docetaxel and enzalutamide, against bone metastatic castration-resistant PCa.
The effects of mifepristone, alone or in combination with docetaxel or enzalutamide, on PCa cell viability, in vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc tumors in athymic nude mice was used to evaluate the in vivo efficacy of mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and radiography.
Although mifepristone exhibits a certain degree of synergism with docetaxel or enzalutamide in cell culture, statistical analyses showed that combination regimens fail to demonstrate effectiveness in suppressing the skeletal growth of PCa and enhancing the in vivo efficacy of docetaxel or enzalutamide in athymic nude mice (p>0.05).
These results provide the first pre-clinical evidence suggesting that mifepristone may not effectively inhibit bone metastatic PCa, either as a single agent or combined with standard chemotherapy and androgen-deprivation therapy. This report may raise concerns over the clinical use of mifepristone in the management of advanced PCa.
米非司酮作为一种新型抗癌药物，包括对前列腺癌（PCa）的潜在作用，已引起广泛关注。然而，最近在PCa和其他癌症中使用米非司酮的临床试验结果令人失望。我们评估了米非司酮联合多西他赛和恩杂鲁胺对骨转移性去势抵抗性PCa的体外和体内活性。
采用比色法测定米非司酮单独或联合多西他赛或恩杂鲁胺对PCa细胞活力的体外影响。利用无胸腺裸鼠的胫骨内C4-2-Luc肿瘤模型评估米非司酮单独或联合多西他赛或恩杂鲁胺的体内疗效。通过血清前列腺特异性抗原（PSA）水平和X线摄影评估小鼠骨骼中的肿瘤生长情况。
虽然在细胞培养中米非司酮与多西他赛或恩杂鲁胺表现出一定程度的协同作用，但统计分析表明，联合用药方案在抑制PCa骨骼生长和增强多西他赛或恩杂鲁胺在无胸腺裸鼠体内的疗效方面未能显示出有效性（p>0.05）。
这些结果提供了首个临床前证据，表明米非司酮无论是作为单一药物还是与标准化疗及雄激素剥夺疗法联合使用，都可能无法有效抑制骨转移性PCa。本报告可能会引发对米非司酮在晚期PCa治疗中临床应用的担忧。
