Lycopene enhances the sensitivity of castration-resistant prostate cancer to enzalutamide through the AKT/EZH2/androgen receptor signaling pathway

作者全名："Chen, Xiong; Yang, Guo; Liu, Miao; Quan, Zhen; Wang, Leilei; Luo, Chunli; Wu, Xiaohou; Zheng, Yongbo"

作者地址："[Chen, Xiong; Yang, Guo; Liu, Miao; Quan, Zhen; Wu, Xiaohou; Zheng, Yongbo] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Wang, Leilei; Luo, Chunli] Chongqing Med Univ, Coll Lab Med, Chongqing, Peoples R China; [Chen, Xiong] Ninth Peoples Hosp Chongqing, Dept Urol Surg, Chongqing, Peoples R China"

通信作者："Wu, XH; Zheng, YB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Urol Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000878132700009

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：613

期号：　

开始页：53

结束页：60

文献类型：Article

关键词：Lycopene; Enzalutamide; Castration-resistant prostate cancer; Androgen receptor; AKT; EZH2

摘要："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 downregulated in 22RV1 and C4e2B 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. (C) 2022 Elsevier Inc. All rights reserved."

基金机构：National Natural Science Foundation of China (NSFC) [81802543]

基金资助正文：This study is one of the projects of the National Natural Science Foundation of China (NSFC) (Grant No.81802543).