Potential therapeutic effect of epigenetic therapy on Ireatment-induced neuroendocrine prostate cancer  

作　　者：Xiang Xu Yu-Hua Huang Yan-Jing Li Alexa Cohen Zhen Li Jill Squires Wei Zhang Xu-Feng Chen Min Zhang Jiao-Ti Huang 

机构地区：[1]School of Life Sciences, Anhui University, Hefei, China [2]Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA [3]Department of Urology, The First Affiliated Hospital of SooChow University, Suzhou, China [4]Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA [5]Department of Pathology, Beijing Hospital, Beijing, China

出　　处：《Asian Journal of Andrology》2017年第6期686-693,共8页亚洲男性学杂志（英文版）

摘　　要：Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model （LNCaP/NE1.8） to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model （LNCaP/NE1.8） to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

关 键 词：cancer stem cell epigenetic therapy hormonal therapy neuroendocrine prostate cancer suberoylanilide hydroxamic acid 

分 类 号：S816.7[农业科学—饲料科学] TQ245.23[农业科学—畜牧学]