• 关键词：TBBPA  人子宫内膜癌  上皮间充质转化(EMT)  细胞侵袭  细胞迁移

• 基金项目：国家自然科学基金（No.31770382）；国家自然科学基金青年基金（No.21707085，81603020）；山西省青年科技基金（No.201701D221244）；山西省"1331计划"协同创新中心和团队项目

• 刘小娜
• 山西大学生物技术研究所, 太原 030006

• 晋小婷
• 山西大学生物技术研究所, 太原 030006

• 苏瑞军
• 山西大学生物技术研究所, 太原 030006

• 郭松佳
• 山西省人民医院精准医学中心, 太原 030012

• 李汉卿
• 山西大学生命科学学院, 太原 030006

• 李卓玉
• 1. 山西大学生物技术研究所, 太原 030006;2. 山西大学生物医学研究学院, 太原 030006;3. 山西大学生命科学学院, 太原 030006

• 摘要：为了研究低浓度四溴双酚A （TBBPA）暴露对人子宫内膜癌恶化的影响，本实验采用人子宫内膜癌细胞Ishikawa暴露于不同浓度的TBBPA，探讨其毒性效应及可能存在的分子机理.实验采用MTT法检测Ishikawa细胞的存活率，用倒置显微镜观察TBBPA对Ishikawa细胞形态的影响，用细胞划痕与Transwell实验检测细胞迁移侵袭情况，用实时荧光定量PCR与Western blotting分别检测上皮间充质转化（Epithelial Mesenchymal Transition，EMT）标志物及相关转录因子mRNA与蛋白水平表达量.结果显示，Ishikawa细胞暴露于不同浓度TBBPA （1.00×10^-9、1.00×10^-8、1.00×10^-7 mol·L^-1）后，细胞存活率明显升高，细胞形态由卵圆形逐渐变为长梭形，细胞侵袭率、细胞划痕愈合率、细胞迁移率与对照组相比显著升高，差异具有统计学意义.在mRNA和蛋白水平上，EMT标志物E-cadherin表达量显著下降，Vimentin和N-cadherin表达量明显上升；EMT上游转录因子Twist和Snail-1的含量也显著增加.结果表明，TBBPA暴露是通过改变细胞内E-cadherin、Vimentin和N-cadherin的含量进而激活Ishikawa细胞上皮间充质转化，导致人子宫内膜癌的恶化；而激活上皮间充质转化的过程可能与TBBPA诱导Twist和Snail-1的表达有关.

• Abstract：This study aims to investigate the effect of low concentration TBBPA on deterioration of human endometrial carcinoma and the possible molecular mechanism, Ishikawa cells were exposed with different concentrations of TBBPA. The cell viability rate of Ishikawa cells was measured by MTT assay. The morphology of cells after TBBPA exposure was observed by inverted microscope. The cell migration and invasion were detected by cell scratch and Transwell assay. The mRNA levels of epithelial mesenchymal transition (EMT) markers and related transcription factors were detected by real-time fluorescence quantitative PCR, and their protein levels were analyzed by Western blotting. The data indicated that the cell viability rate was significantly increased and the morphology of cells was changed from oval to long fusiform after TBBPA exposure. The cell invasion rate, the cell scratch healing rate and the cell migration rate in TBBPA-exposed groups were significantly higher than control group. For EMT markers, E-cadherin expression decreased,but the expression of Vimentin and N-cadherin increased significantly in both mRNA and protein levels. The contents of the upstream transcription factors Twist and Snail-1 in EMT also increased remarkably. Our results suggest that TBBPA exposure can activate EMT by alterations of E-cadherin, Vimentin and N-cadherin in Ishikawa cells, which eventually lead to the deterioration of human endometrial carcinoma. The activation of EMT may be related to TBBPA induced Twist and Snail-1 expression.

• Key words：TBBPA  human endometrial carcinoma  EMT  invasion  migration

• 
  摘要点击次数： 829 全文下载次数： 878