Wang Yanru, Zhang Shumin, Iqbal Shareen, Chen Zhengjia, Wang Xiaojing, Wang Yongqiang A, Liu David, Bai Kevin, Ritenour Chad, Kucuk Omer, Wu Daqing
Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Prostate. 2013 Dec 23. doi: 10.1002/pros.22769.
Docetaxel treatment is the only first-line chemotherapy with a survival benefit in metastatic castration-resistant prostate cancer (PCa). Nonetheless, most patients become docetaxel resistant and inevitably progress with no cure. In this study, we investigated the potential of pomegranate extract (PE) in targeting metastatic castration-resistant PCa and improving docetaxel chemotherapy.
The in vitro and in vivo effect of POMx, a PE formula currently approved for clinical trials, in metastatic castration-resistant PCa cells was evaluated in experimental models.
We demonstrated that POMx exhibited potent in vitro cytotoxicity in metastatic castration-resistant PCa cells. Mechanistic studies identified survivin as a novel molecular target that may mediate the anti-cancer activity of POMx, presumably through the inhibition of signal transducer and activator of transcription 3. The in vivo administration of POMx treatment effectively inhibited survivin, induced apoptosis, retarded C4-2 tumor growth in skeleton and significantly enhanced the efficacy of docetaxel in athymic nude mice.
These results provide the first preclinical evidence that POMx may be effective in treating metastatic castration-resistant PCa and enhancing the efficacy of docetaxel chemotherapy. Prostate © 2013 Wiley Periodicals, Inc.
多西他赛治疗是转移性去势抵抗性前列腺癌（PCa）中唯一具有生存获益的一线化疗方法。然而，大多数患者会对多西他赛产生耐药，最终不可避免地病情进展且无法治愈。在本研究中，我们探究了石榴提取物（PE）针对转移性去势抵抗性PCa以及改善多西他赛化疗效果的潜力。
在实验模型中评估了目前已获批用于临床试验的PE配方POMx对转移性去势抵抗性PCa细胞的体外和体内作用。
我们证明POMx在转移性去势抵抗性PCa细胞中表现出强大的体外细胞毒性。机制研究确定生存素是一种新的分子靶点，可能介导POMx的抗癌活性，推测是通过抑制信号转导和转录激活因子3来实现。在无胸腺裸鼠体内给予POMx治疗可有效抑制生存素、诱导细胞凋亡、延缓骨骼中C4 - 2肿瘤生长，并显著增强多西他赛的疗效。
这些结果提供了首个临床前证据，表明POMx可能有效治疗转移性去势抵抗性PCa并增强多西他赛化疗的疗效。前列腺 © 2013威利期刊公司。
