MAOA在诱导前列腺癌神经内分泌分化中的作用  

The Function of MAOA in Inducing the Neuroendocrine Differentiation of Prostate Cancer

作　　者：税雪 许荣 谢清华 张彩勤 谭邓旭 师长宏 赵菊梅[1] SHUI Xue;XU Rong;XIE Qinghua;ZHANG Caiqin;TAN Dengxu;SHI Changhong;ZHAO Jumei(Medical College of Yan'an University,Yan'an 716000,China;Laboratory Animal Center,the Air Force Medical University,Xi'an 710032,China)

机构地区：[1]延安大学医学院,延安716000 [2]空军军医大学实验动物中心,西安710032

出　　处：《实验动物科学》2021年第4期40-46,共7页Laboratory Animal Science

基　　金：国家自然科学基金(No.32070532)。

摘　　要：目的建立神经内分泌性前列腺癌(neuroendocrine prostate cancer,NEPC)细胞模型和动物模型,探讨单胺氧化酶A(monoamine oxidase A,MAOA)在前列腺癌神经内分泌分化(neuroendocrine transdifferentiation,NED)中的作用及机制。方法选取人前列腺癌细胞系C4-2,通过恩杂鲁胺(enzalutamide,ENZ)长期诱导获得NEPC细胞模型;通过酶活性实验、Real-time PCR和Western blot技术检测NED过程中MAOA的水平变化;使用MAOA抑制剂氯吉灵(clorgyline,CLG)检测MAOA对神经内分泌标志物的影响并探讨其潜在机制;建立前列腺癌异种移植模型,体内实验验证MAOA与NED之间的相关性。结果ENZ可作为诱导NEPC模型的方法;在ENZ引起的NED过程中,MAOA的表达和活性增加;抑制MAOA的活性可以延缓NED的发生,这可能是MAOA通过抑制缺氧信号实现的。结论MAOA是促进NED和维持神经内分泌细胞特性的关键靶点,MAOA抑制剂CLG可以延缓NEPC发生,可能作为前列腺癌患者的潜在治疗药物。Objective The cell and animal model of neuroendocrine prostate cancer(NEPC)were established respectively to explore the function and mechanism of monoamine Oxidase A(MAOA)in the neuroendocrine transdifferentiation(NED)of prostate cancer(PCa).Method Human prostate cancer cell lines C4-2 were selected to establish the cell model of NEPC by long-term induction of Enzalutamide(ENZ)treatment.The change of MAOA expression was detected by the enzyme activity experiment,and the marker of neuroendocrine differentiation were analyzed by Real-time fluorescent quantitative PCR and Western blot technology.The PCa cells22 RV1 were implanted subcutaneously into nude mice to establish xenograft model and to observe the effect of MAOA inhibitor clorgyline(CLG)on neuroendocrine markers,to explore its underlying mechanism.Result ENZ could be used to induce the NEPC cell model.During the process of NED,the expression and activity of MAOA was increased.When CLG inhibit the activity of MAOA in the NEPC animal model the process of NED was delayed.The reason may be MAOA suppression of hypoxia relative signal.Conclusion MAOA is a key target to promote NED and maintain the characteristics of neuroendocrine cells.MAOA inhibitor CLG could delay the occurrence of NEPC and may be a new potential therapeutic drug for prostate cancer patients.

关 键 词：神经内分泌性前列腺癌 MAOA 恩杂鲁胺 氯吉灵 

分 类 号：R-96[医药卫生]