【摘要】 建立前列腺癌细胞系模拟雄激素剥夺疗法(ADT)后前列腺癌细胞的转化状态,评估去势抵抗性前列腺癌(CRPC)转变过程中参与细胞代谢的脂类和能量蛋白的表达变化,探讨其对CRPC细胞的调节作用。用雄激素依赖性LNCaP细胞系在无雄激素环境下培养获得雄激素非依赖性LNCaP-R,通过双向凝胶电泳(2-DE)及质谱分析评估这两个同源细胞系中参与代谢相关蛋白的表达变化。结果 LNCaP及LNCaP-R间蛋白质存在差异表达;其中参与脂类和能量代谢通路的蛋白表达差异明显。参与能量和脂类等细胞代谢的蛋白在前列腺癌去势后发生明显变化,生长抑素以及他汀类(Statins)药物对该类蛋白的抑制作用,有可能通过调节前列腺癌细胞的新陈代谢和线粒体功能,可作为治疗CRPC的潜在辅助药物应用于临床。更多还原

【Abstract】 To imitate the clinical progression of prostate cancer from androgen sensitive to androgen independent state after androgen deprivation therapy(ADT),a LNCaP-R cell line model was established from LNCaP cells.The cellular metabolism pathways and related protein expression alterations were explored on the effects on the castration-resistant prostate cancer(CRPC).A LNCaP-R cell line was cultured from a parental prostate cancer cell line LNCaP in a androgen deprivation condition.Two-dimensional gel electrophoresis(2-DE)followed by MALDI-TOF mass spectrometric analysis were used to evaluate differentially expressed proteins of the parental LNCaP cells and LNCaP-R cells after androgen deprivation therapy.A series of proteins were identified differentially expressed in LNCaP cells and LNCaP-R cells.Important proteins related to energy and lipid metabolism pathways(e.g.GRP78,HSPD1,CKB,PRDX1)were found to be involved in the CRPC progression.LNCaP-R cells as potential metastatic androgen independent cancer cells,its metabolism and mitochondrial functions could be altered by Statins,which possibly lead to the introduction of a novel combinational therapeutic approach for CRPC.更多还原