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Abstract

Background and Objective: Clinical studies have shown that castration-resistant prostate cancer (CRPC) is the ultimate cause of death in men with advanced prostate cancer. Among them long-term androgen deprivation therapy (ADT)-induced neuroendocrine differentiation (NED) and neuroendocrine prostate cancer (NEPC) are most important causes to CRPC. NED is a kind of undifferentiated small cell carcinoma with high-invasiveness which could be induced by long time ADT, leading to a highly invasive and metastatic clinical process. Therefore, it is a current research hotspot to develop targeted therapeutic drug for NED. This study aimed to investigate the role of propranolol in the progression of NED induced by ADT and the related mechanisms. Materials and Methods: Androgen receptor (AR) antagonist enzalutamide (MDV3100) was used to induce androgen deprivation. MTT and cell migration assays were performed to assess the effect of propranolol on cell viability and migration. Western Blot was used to measure the expression of NED/NEPC biomarkers such as CHGA, ENO2 as well as CREB (cAMP response element binding protein) and phosphorylation level of CREB (p-CREB). A qRT-PCR was performed to test the mRNA level of CHGA, ENO2, KLK3. Results: ADT promoted prostate cancer cell growth and migration, up-regulated the CHGA expression and down-regulated AR expression. Propranolol could reverse the NED progression through inhibiting CREB phosphorylation and finally down-regulating CHGA expression. Conclusion: Propranolol might suppress the progression of NED via inhibiting CREB phosphorylation possibly.