沉默同源异型盒基因2表达对乳腺癌紫杉醇化疗敏感性的影响及分子机制  

Effects of Prrx2 gene silencing on paclitaxel chemosensitivity of breast cancer and its molecular mechanism

作　　者：吕志栋[1] 潘立峰 刘芳[1] 聂刚[1] 窦榕榕[1] 赵宁[3] 李福年[1] Lyu Zhidong;Pan Lifeng;Liu Fang;Nie Gang;Dou Rongrong;Zhao Ning;Li Funian(Breast Disease Diagnosis and Treatment Center,Affiliated Hospital of Qingdao University,Qingdao 266000,China;Department of Cardiology,Shandong Second People’s Hospital,Ji’nan 250023,China;Western Coast Hospital Breast Surgery,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]山东省第二人民医院心内科,济南250023 [3]青岛大学附属医院西海岸院区乳腺外科,青岛266000

出　　处：《中华转移性肿瘤杂志》2022年第2期158-162,共5页Chinese Journal of Metastatic Cancer

基　　金：中国博士后基金面上项目(2020M672001);山东省自然科学基金面上项目(ZR2020MH274);山东省医药卫生发展计划项目(2019WS112)。

摘　　要：目的观察沉默同源异型盒基因2(Prrx2)表达后对乳腺癌紫杉醇化疗敏感性的影响及相关机制。方法选取Prrx2表达较高的MCF-7和MDA-MB-231细胞作为研究对象,构建稳定沉默Prrx2表达的细胞株。采用不同浓度的紫杉醇作用于癌细胞,分析肿瘤细胞增殖、克隆形成和半数抑制浓度(IC50)变化。构建裸鼠移植瘤模型,分析沉默Prrx2表达后紫杉醇对移植瘤生长的影响。RT-PCR检测凋亡相关基因的变化。结果沉默Prrx2表达后MCF-7、MDA-MB-231细胞紫杉醇IC50明显降低,并提高紫杉醇对裸鼠移植瘤生长抑制作用。沉默Prrx2表达后促进紫杉醇诱导的癌细胞凋亡,可能与Bcl-2、Bax表达异常有关。蛋白检测发现沉默Prrx2表达下调β-catenin在乳腺癌细胞核中的表达,抑制Wnt/β-catenin信号通路的活性。结论沉默Prrx2表达后增强乳腺癌细胞对紫杉醇化疗敏感性,可能与下调Wnt/β-catenin信号通路活性有关。Objective To observe the effect of silencing Paired-related homeobox 2(Prrx2)on paclitaxel chemosensitivity of breast cancer and its molecular mechanism.Methods Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2.Different concentrations of paclitaxel were used to treat cancer cells.The changes of cell cloning,IC50 and cell cycle were analyzed.A nude mouse model of transplanted tumor was established to analyze the effect of paclitaxel on the growth of transplanted tumor after silencing the expression of Prrx2.RT-PCR was used to detect the changes of apoptosisrelated genes.Results After silencing Prrx2 expression,the IC50 of paclitaxel in MCF-7 and MDA-MB-231 decreased significantly,and the inhibitory effect of paclitaxel on transplanted tumor in nude mice was enhanced.Silencing of Prrx2 promoted apoptosis induced by paclitaxel,which may be related to the abnormal expression of Bcl-2 and Bax.Western blot showed that silencing of Prrx2 inhibited the expression ofβ-catenin in breast cancer and down-regulated the activity of Wnt/β-catenin signaling pathway.Conclusions Silencing of Prrx2 enhance the chemosensitivity of breast cancer to paclitaxel chemotherapy,which may be related to the decrease of Wnt/β-catenin signaling pathway.

关 键 词：乳腺肿瘤 同源异型盒基因2 紫杉醇 增殖 

分 类 号：R737.9[医药卫生—肿瘤]