摘要
目的探索前列腺癌神经内分泌分化(neuroendocrine differentiation,NED)进展中单胺氧化酶A(monoamine oxidase A,MAOA)和叉头框蛋白A1(forkhead box A1,FOXA1)的动态变化特征,为临床神经内分泌型前列腺癌(neuroendocrine prostate cancer,NEPC)的治疗提供新的策略。方法通过恩杂鲁胺(enzalutamide,ENZ)长期持续诱导的方式建立NED的细胞模型和小鼠移植模型;采用Western Blot和Real-time PCR方法检测MAOA、FOXA1在NED中的动态表达;选用GEO数据库分析在多种NED模型中MAOA与FOXA1的动态变化趋势;构建前列腺癌细胞系小鼠移植模型,通过免疫组化分析体内模型中MAOA、FOXA1在NED中的动态表达;通过慢病毒转染干预MAOA,检测MAOA对FOXA1的调控作用。结果MAOA与FOXA1在NED过程中均呈现先升高后降低的动态变化特征;敲低前列腺癌细胞中MAOA可以导致FOXA1的表达降低,这可能是MAOA通过FOXA1在NED的不同阶段发挥不同作用。结论MAOA和FOXA1在NED过程中呈先升高后降低的趋势,MAOA的表达能影响FOXA1的水平,MAOA/FOXA1可能在NED过程中发挥动态调控的作用。
Objective To explore the dynamic changes in monoamine oxidase A(MAOA)and forkhead box A1(FOXA1)levels during neuroendocrine differentiation(NED)in prostate cancer,providing new strategies for the treatment of neuroendocrine prostate cancer.Methods Cell models and mouse transplantation models of NED were established through long⁃term sustained induction with enzalutamide(ENZ).Dynamic expression of MAOA and FOXA1 in NED was detected by Western Blot and Real⁃time PCR.GEO database data were selected to analyze the dynamic trends in MAOA and FOXA1 levels in multiple NED models.We constructed a mouse transplantation model of human prostate cancer cell lines and analyzed the dynamic expression of MAOA and FOXA1 in the in vivo NED model by immunohistochemistry.MAOA expression was disrupted with lentiviral transfection,and the impact on FOXA1 was detected.Results Both MAOA and FOXA1 concentrations showed dynamic characteristics,increasing and then decreasing during the NED process.Knockdown of MAOA in prostate cancer cells led to decreased expression of FOXA1.This MAOA may play different roles at different stages of NED by acting through FOXA1.Conclusions Both MAOA and FOXA1 levels showed increasing,then decreasing,trends during NED.The expression of MAOA affected the level of FOXA1,and MAOA/FOXA1 may play a dynamic regulatory role in the NED process.
作者
韩昊
李惠
张彩勤
赵菊梅
魏晓丽
师长宏
HAN Hao;LI Hui;ZHANG Caiqin;ZHAO Jumei;WEI Xiaoli;SHI Changhong(Medical College of Yan’an University,Yan’an 716000,China;Laboratory Animal Center,the Air Force Medical University,Xi’an 710032,China)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2024年第6期683-690,共8页
Acta Laboratorium Animalis Scientia Sinica
基金
国家自然科学基金(32070532,32270566)。
