Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Prostate. 2013 Nov;73(15):1681-9. doi: 10.1002/pros.22705. Epub 2013 Sep 2.
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.
The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models.
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.
This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC.
卡巴他赛（Jevtana）已被批准用于治疗转移性去势抵抗性前列腺癌（mCRPC）。然而，大多数患者会出现进展并产生耐药性，这仍然是晚期前列腺癌治疗的主要挑战。在这项研究中，我们研究了大豆异黄酮染料木黄酮是否可以在实验模型中增强 mCRPC 细胞对卡巴他赛治疗的敏感性。
在实验模型中评估了染料木黄酮增强 mCRPC 细胞对卡巴他赛化疗反应的体外和体内作用。
染料木黄酮增加了促凋亡蛋白 Bax 的表达，激活了凋亡信号，并增强了 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，与载体对照、卡巴他赛或染料木黄酮相比，染料木黄酮和卡巴他赛联合治疗显著延缓了 mCRPC 的生长。组织染色证实了染料木黄酮在体内诱导 Bax 和激活细胞凋亡的作用。
这项研究提供了首个支持染料木黄酮可改善 mCRPC 中卡巴他赛化疗的临床前证据。
