沉默同源异型盒基因2表达对乳腺癌增殖的影响及其分子机制  

Effects of Prrx2 gene silencing on the proliferation of breast cancer and its molecular mechanisms

作　　者：吕志栋[1] 杨召川[2] 金丽英[3] 聂刚[1] 王圆媛 孔滨 王海波[1] Lii Zhidong;Yang Zhaochuan;Jin Liying;Nie Gang;Wang Yuanyuan;Kong Bin;Wang Haibo(Breast Centre,the Affiliated Hospital of Qingdao Universityy Qingdao 266000,China;Departments of Child Health Care,the Affiliated Hospital of Qingdao University,Qingdao 266000,China;Cerebrovascular Disease Research Institute,the Affiliated Hospital of Qingdao University,Qingdao 266000,China)

机构地区：[1]青岛大学附属医院乳腺病诊疗中心,青岛266000 [2]青岛大学附属医院儿童保健科,青岛266000 [3]青岛大学附属医院脑科研究所,青岛266000

出　　处：《中华医学杂志》2020年第12期942-946,共5页National Medical Journal of China

基　　金：国家自然科学基金(81700029);青岛市应用基础研究计划项目(19-6-2-54-cg);齐鲁卫生与健康领军人才项目。

摘　　要：目的观察沉默同源异型盒基因2(Prrx2)表达后对乳腺癌细胞增殖和肿瘤生长的影响及其分子机制。方法以人乳腺癌细胞系MCF-7、MDA-MB-231作为研究对象,构建稳定沉默Prrx2表达的细胞株。采用MTT法分析癌细胞的增殖情况;裸鼠移植瘤实验观察沉默Prrx2表达对肿瘤生长的影响;Western印迹分析沉默Prrx2表达后β-连环链蛋白(catenin)在细胞内的分布变化。结果转染干扰载体后MDA-MB-231细胞Prrx2表达下降91.2%;MCF-7细胞表达下降88.7%,差异均具有统计学意义(P<0.05)。MTT实验显示沉默Prrx2表达后癌细胞的增殖能力明显减弱,差异具有统计学意义(P<0.05)。裸鼠移植瘤实验发现沉默组的移植瘤体重量明显小于空白载体组(160.2±26.3)mg与(365.4±19.7)mg,差异有统计学意义(P<0.05)。Western印迹检测发现沉默Prrx2表达可抑制β-catenin在乳腺癌细胞核中的表达,下调Wnt/β-catenin信号通路的活性。结论沉默Prrx2表达可有效抑制乳腺癌的增殖和肿瘤生长能力,针对Prrx2的治疗可能成为治疗乳腺癌的新靶点。Objective The aim of this study was to investigate the effects of silencing Paired related homoeobox 2(Prrx2)expression on the proliferation of breast cancer and its molecular mechanisms.Methods Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2.The level of Prrx2 was verified by Western blot.MTT assay was used to analyze the proliferation of breast cancer cells in vitro.To investigate the effect of Prrx2 depletion on tumor growth in vivo,a nude mouse xenograft model was performed.Results The expression of Prrx2 decreased 91.2%in MDA-MB-231 cells and 88.7%in MCF-7 cells after transfection with interfering vectors(P<0.05).MTT assay showed that the proliferation of cells in silenced Prrx2 expression group was significantly inhibited compared with the control group(P<0.05).Nude mice transplanted tumors showed that the growth of transplanted tumors was slow after silencing Prrx2 expression,and the weight of the tumors of silenced Prrx2 expression group were smaller than those of the control group((160.2±26.3)mg vs(365.4±19.7)mg,P<0.05).Western blot showed that silencing Prrx2 expression inhibited the expression ofβ-catenin in breast cancer cell nucleus and down-regulated the activity of Wnt/β-catenin signaling pathway.Conclusions Silencing Prrx2 expression can effectively inhibit the proliferation and growth of breast cancer,suggesting that Prrx2 may become a new target for the treatment of breast cancer.

关 键 词：乳腺肿瘤 同源异型盒基因2 增殖 信号通路 

分 类 号：R737[医药卫生—肿瘤]