Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University. No.1, Youyi Road, Chongqing, 400016, PR China; Department of Urology Surgery, The Ninth People's Hospital of Chongqing, Chongqing, PR China.
Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University. No.1, Youyi Road, Chongqing, 400016, PR China.
Biochem Biophys Res Commun. 2022 Jul 12;613:53-60. doi: 10.1016/j.bbrc.2022.04.126. Epub 2022 Apr 30.
Enzalutamide is an effective drug for the treatment of castration-resistant prostate cancer (CRPC), but acquired enzalutamide resistance is usually unavoidable within the short term in many patients. Lycopene, a safe and effective phytochemical, has been documented to have anticancer activity in a variety of tumors, especially for prostate cancer (PCa). The aim of this study was to provide data support for the combination of lycopene and enzalutamide in the treatment of CRPC. To this end, tissues from patients with primary prostate cancer (PPC) and CRPC were examined by immunohistochemical analysis and found that p-AKT and p-EZH2 were overexpressed in CRPC. Furthermore, Kaplan-Meier survival analysis showed that the high expression of p-AKT and p-EZH2 may be related to the poor prognosis of patients. In addition, the expression of p-AKT, p-EZH2 and androgen receptor (AR) were significantly down-regulated in 22RV1 and C4-2B cells and the proliferation and invasion of CRPC cells were inhibited after treatment with lycopene, while SC79 (an AKT agonist) markedly rescue this effect. Of note, a combination of lycopene and enzalutamide significantly inhibited the proliferation and invasion of CRPC cells in vitro, as well as tumor growth and bone metastasis in vivo. These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.
恩扎卢胺是一种有效的治疗去势抵抗性前列腺癌（CRPC）的药物，但在许多患者中，短期内通常不可避免地会出现获得性恩扎卢胺耐药性。番茄红素是一种安全有效的植物化学物质，已被证明在多种肿瘤中具有抗癌活性，尤其是前列腺癌（PCa）。本研究旨在为番茄红素与恩扎卢胺联合治疗 CRPC 提供数据支持。为此，通过免疫组织化学分析检查了原发性前列腺癌（PPC）和 CRPC 患者的组织，发现 p-AKT 和 p-EZH2 在 CRPC 中过表达。此外，Kaplan-Meier 生存分析表明，p-AKT 和 p-EZH2 的高表达可能与患者的不良预后有关。此外，在 22RV1 和 C4-2B 细胞中，p-AKT、p-EZH2 和雄激素受体（AR）的表达明显下调，番茄红素处理后 CRPC 细胞的增殖和侵袭受到抑制，而 SC79（一种 AKT 激动剂）则明显挽救了这种作用。值得注意的是，番茄红素和恩扎卢胺的联合使用显著抑制了 CRPC 细胞在体外的增殖和侵袭，以及体内的肿瘤生长和骨转移。这些结果表明，番茄红素通过抑制 AKT/EZH2 通路降低 AR 蛋白水平，增强了恩扎卢胺的抗肿瘤作用，这可能为提高恩扎卢胺在 CRPC 中的疗效提供一种新方法。
