胞孢子酮B对雄激素剥夺促发的前列腺癌细胞侵袭的逆转作用和机制  

The reverse effects of cytosporone B on androgen deprivation therapy-induced invasion of prostate cancer cells and its mechanism

作　　者：王建 丁聪聪 陆岩 WANG Jian;DING Congcong;LU Yan(Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,Guangdong Medical University,Dongguan 523808,China)

机构地区：[1]广东医科大学广东省医学分子诊断重点实验室,广东东莞523808

出　　处：《中国病理生理杂志》2023年第8期1408-1414,共7页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No.2018A030307039);广东医科大学重点培育项目(No.GDMUZ2019006)。

摘　　要：目的:探讨胞孢子酮B(cytosporone B,Csn-B)对雄激素剥夺治疗所促发的前列腺癌细胞侵袭的作用和分子机制。方法:培养人雄激素依赖性前列腺癌细胞系LNCaP并加药处理,实验分为对照(control)组、Caso⁃dex(抗雄激素药物)组、MDV3100(雄激素受体拮抗剂)组、Csn-B+Casodex组和Csn-B+MDV3100组。通过Transwell法检测各组细胞的侵袭能力;分别提取细胞核和细胞质组分,并应用Western blot法检测神经生长因子诱导克隆B(nerve growth factor-induced clone B,NGFI-B/Nur77)蛋白水平;通过RT-qPCR和Western blot法分别检测基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)的mRNA及蛋白表达水平;分别提取微管蛋白β-tubulin的聚合和游离组分,通过Western blot法检测其表达水平。结果:与control组相比,Casodex组和MDV3100组LNCaP细胞的侵袭能力显著增强,胞核和胞质中Nur77蛋白水平均显著下调,MMP-9的mRNA和蛋白表达水平显著上调,β-tubulin蛋白的聚合/游离(polymerized/soluble,P/S)比值显著减小(P<0.05);分别与Casodex组和MDV3100组相比,Csn-B+Ca⁃sodex组和Csn-B+MDV3100组LNCaP细胞侵袭能力显著减弱,胞核和胞质中Nur77蛋白水平均显著上调,MMP-9的mRNA和蛋白表达水平显著下调,β-tubulin蛋白的P/S值显著增大(P<0.05或P<0.01)。结论:胞孢子酮B能逆转雄激素剥夺促发的前列腺癌细胞侵袭,其机制可能依赖于Nur77蛋白分别在细胞核和细胞质中主导的双重分子通路。AIM:To investigate the role of cytosporone B(Csn-B)in androgen deprivation therapy-induced invasion of prostate cancer cells and its molecular mechanism.METHODS:Human androgen-dependent prostate cancer LNCaP cells were constructed and treated with drugs.The cells were divided into control group,Casodex(an antiandrogen)group,MDV3100(an androgen receptor antagonist)group,Csn-B+Casodex group and Csn-B+MDV3100 group.The cell invasive ability was assessed by Transwell assay.The nuclear and cytoplasmic nerve growth factor-induced clone B(NGFI-B/Nur77)fractions,protein expression of matrix metalloproteinase-9(MMP-9),and the polymerized and solubleβ-tubulin fractions were analyzed using Western blot.RT-qPCR was used detected the mRNA expression of MMP-9.RESULTS:Compared with control group,the cell invasive ability was increased,the protein levels of the nuclear and cytoplasmic Nur77 fractions were down-regulated,the mRNA and protein expression levels of MMP-9 were up-regulated,and the polymerized/soluble(P/S)ratio ofβ-tubulin was reduced in both Casodex group and MDV3100 group(P<0.05).However,the cell invasive ability was decreased,the protein levels of the nuclear and cytoplasmic Nur77 fractions were up-regulated,the mRNA and protein expression levels of MMP-9 were down-regulated,and the P/S ratio ofβ-tubulin was increased in both Csn-B+Casodex group and Csn-B+MDV3100 group compared with Casodex group and MDV3100 group,respectively(P<0.05 or P<0.01).CONCLUSION:Cytosporone B can reverse androgen deprivation therapy-induced invasion of prostate cancer cells by two independent pathways,dominated by Nur77 in the nucleus and cytoplasm,respectively.

关 键 词：胞孢子酮B 前列腺癌 雄激素剥夺疗法 细胞侵袭 

分 类 号：R737.25[医药卫生—肿瘤] R363[医药卫生—临床医学]