碱性亮氨酸拉链和W2结构域2对子宫内膜癌细胞生物学行为的作用及机制  

Role of basic leucine zipper and W2 domains 2 on the biological behaviors of endometrial cancer cells and its mechanism

作　　者：唐彬 蔡文 徐姗姗[1] 江征慧 未亚兰 江飞云 TANG Bin;CAI Wen;XU Shanshan;JIANG Zhenghui;WEI Yalan;JIANG Feiyun(Department of Gynecology,East China Normal University Affiliated Wuhu Hospital,the Second People′s Hospital of Wuhu City in Anhui Province,Wuhu,Anhui,241000)

机构地区：[1]华东师范大学附属芜湖医院/安徽省芜湖市第二人民医院妇科,安徽芜湖241000

出　　处：《实用临床医药杂志》2023年第18期18-25,共8页Journal of Clinical Medicine in Practice

基　　金：安徽省芜湖市科技计划项目(2021cg47)。

摘　　要：目的 探讨碱性亮氨酸拉链和W2结构域2(BZW2)对子宫内膜癌细胞增殖、侵袭、迁移及细胞周期的调控作用及其潜在作用机制。方法 采用实时荧光定量聚合酶链反应(RT-qPCR)、蛋白质印迹法(Western blot)检测BZW2在人子宫内膜基质细胞系ESC和人子宫内膜癌细胞(Ishikawa、KLE、RL95-2、HEC-1-A)中的表达。将BZW2干扰质粒转染至HEC-1-A细胞,并加入Wnt/β-连环蛋白(Wnt/β-catenin)信号通路激动剂SKL2001进行处理。采用CCK-8、克隆形成实验、划痕实验及Transwell实验分别检测细胞活性、克隆形成、迁移及侵袭能力;采用流式细胞术检测细胞周期;采用GSEA分析BZW2在Wnt信号通路中的富集度;采用Western blot分析增殖、转移、周期及Wnt/β-catenin通路相关蛋白表达水平。结果 BZW2在子宫内膜癌细胞中表达上调,干扰BZW2可抑制子宫内膜癌细胞增殖、迁移、侵袭,并诱导G0/G1期细胞阻滞(P<0.001)。敲低BZW2可使Wnt/β-catenin通路失活(P<0.001), SKL2001可部分逆转BZW2缺失对HEC-1-A细胞增殖、迁移、侵袭及细胞周期的调控作用(P<0.001)。结论 BZW2下调可抑制子宫内膜癌细胞增殖、侵袭、迁移,并促进G_(0)/G_(1)期细胞阻滞,其机制可能与Wnt/β-catenin信号通路失活有关,BZW2可作为治疗子宫内膜癌的新靶点。Objective To investigate the regulatory effects of basic leucine zipper and W2 domains 2(BZW2)on proliferation,invasion,migration and cell cycle of endometrial cancer cells and its potential action mechanism.Methods Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the expression of BZW2 in human endometrial stromal cell line ESC and human endometrial cancer cells(Ishikawa,KLE,RL95-2,HEC-1-A).BZW2 interference plasmid was transfected into HEC-1-A cells and treated with Wnt/β-catenin signaling pathway agonist SKL2001.CCK-8,clone formation assay,scratch assay and Transwell assay were used to detect cell activity,colony formation,migration and invasion ability,respectively;the cell cycle was detected by flow cytometry;the concentration of BZW2 in Wnt signaling pathway was analyzed by GSEA;the levels of proliferation,metastasis,cycle and Wnt/β-catenin pathway-related proteins were analyzed by Western blot.Results The expression of BZW2 was up-regulated in endometrial cancer cells,and interference with BZW2 inhibited the proliferation,migration and invasion of endometrial cancer cells,and induced G 0/G 1 cell arrest(P<0.001).BZW2 knockdown inactivated the Wnt/β-catenin pathway(P<0.001),and SKL2001 partially reversed the regulatory effects of BZW2 loss on the proliferation,migration,invasion and cell cycle of HEP-1-A cells(P<0.001).Conclusion[JP3]Down-regulation of BZW2 can inhibit the proliferation,invasion and migration of endometrial cancer cells,and promote G_(0)/G_(1) cell arrest,which may be related to the inactivation of Wnt/β-catenin signaling pathway.BZW2 may be a new target for the treatment of endometrial cancer.

关 键 词：子宫内膜癌 碱性亮氨酸拉链和W2结构域2 细胞周期 迁移 侵袭 WNT/Β-CATENIN信号通路 

分 类 号：R737.33[医药卫生—肿瘤] R73[医药卫生—临床医学]