Prostate, 2013, 73(15):1681-9.

Genistein Enhances the Efficacy of Cabazitaxel Chemotherapy in Metastatic Castration-Resistant Prostate Cancer Cells

Shumin Zhang, Yanru Wang, Zhengjia Chen, et al.

Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia; et al

BACKGROUND:

Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models.

METHODS:

The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models.

RESULTS:

Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis.

CONCLUSION:

This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC.

美国《前列腺》，2013年11月

在转移性去势难治性前列腺癌细胞中金雀异黄素提高了卡巴他赛化疗的疗效

张淑敏，王艳茹，陈正家，等

乔治亚共和国埃默里医科大学泌尿外科和温希普癌症研究所，等

背景︰

卡巴他赛 (Jevtana) 已被批准用于治疗转移性去势难治性前列腺癌 (mCRPC)。然而，大多数病人病情加重并且对药物产生抗性，仍然是目前治疗晚期PCa 的主要挑战。在此研究中，我们探究了在实验模型中金雀异黄素，一种大豆产物富含的异黄酮，是否能使 mCRPC 细胞对卡巴他赛治疗更加敏感。

方法︰

在实验模型中测试了金雀异黄素增强mCRPC 细胞对卡巴他赛化疗反应在体外和体内的疗效。

结果︰

金雀异黄素提高了促凋亡蛋白 Bax 的表达，激活细胞凋亡信号，提高mCRPC 细胞对卡巴他赛治疗的反应。在 PC3-荧光素酶异种移植模型中，金雀异黄素与卡巴他赛的联合治疗明显地减慢了mCRPC的生长，与空白对照样、 卡巴他赛或金雀异黄素相比。组织切片染色证实金雀异黄素诱导 Bax 及细胞凋亡活化的体内作用。

结论︰

这项研究提供第一个临床前证据认为金雀异黄素可能有益于提高卡巴他赛化疗对mCRPC的疗效。