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叉头框蛋白A2对肿瘤细胞迁移、侵袭和上皮-间充质转化的影响

Effects of forkhead box protein A2 on migration,invasion and epithelial mesenchymal transformation of tumor cells
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摘要 目的探讨叉头框蛋白A2(FOXA2)对肿瘤细胞迁移、侵袭和上皮-间充质转化的影响。方法选取河南大学淮河医院2019年6月至2021年10月收治的64例卵巢癌组织和癌旁组织作为研究对象,采用蛋白质免疫印迹分析肿瘤和癌旁组织中FOXA2蛋白表达水平。采用转染试剂转染对照质粒和FOXA2过表达质粒至人卵巢癌细胞SKOV3,分别为对照组和观察组。采用划痕实验、Transwell和蛋白质印迹法(Western blot)分析对照组和观察组细胞迁移、侵袭和上皮-间充质转化能力。采用体外移植瘤实验分析两组细胞的迁移能力。采用荧光定量聚合酶链反应(PCR)分析FOXA2靶基因表达。组间数据比较采用t检验。结果癌旁组织FOXA2蛋白表达水平(1.13±0.24)明显高于卵巢癌组织FOXA2蛋白表达水平(0.47±0.14),差异有统计学意义(t=18.640,P<0.05)。对照组细胞划痕愈合率[(83.67±9.95)%]明显高于观察组细胞划痕愈合率[(56.60±7.06)%],差异有统计学意义(t=5.452,P<0.05)。对照组细胞侵袭数量[(150.83±18.35)个]明显高于观察组细胞划痕愈合率[(84.50±8.89)个],差异有统计学意义(t=7.970,P<0.05)。对照组细胞上皮标志物E-钙黏蛋白(E-cadherin)蛋白表达水平(0.74±0.12)明显低于观察组细胞(1.03±0.16),差异有统计学意义(t=3.626,P<0.05)。对照组细胞间质标志物Snail和N-钙黏蛋白(N-cadherin)蛋白表达水平(1.16±0.12、1.30±0.11)明显高于观察组细胞(0.66±0.08、0.76±0.06),差异有统计学意义(t=8.305、10.300,P<0.05)。对照组细胞淋巴结转移数量[(9.38±1.69)个]明显高于观察组细胞淋巴结转移数量[(3.13±1.46)个],差异有统计学意义(t=7.934,P<0.05)。对照组细胞β-连环蛋白(β-catenin)和c-Myc mRNA表达水平(1.10±0.12、1.23±0.11)明显高于观察组细胞β-catenin和c-Myc mRNA表达水平(0.79±0.08、0.82±0.08),差异有统计学意义(t=5.398、7.305,P<0.05)。结论FOXA2在卵巢癌中呈低表达,通过调节β-catenin和c-Myc表达,参与卵巢癌细胞的迁移、侵袭和上皮-间充质转化的能力。 Objective To investigate the effects of forkhead box protein A2(FOXA2)on the migration,invasion and epithelial mesenchymal transformation of tumor cells.Methods A total of 64 cases of ovarian cancer tissues and adjacent tissues treated in our hospital from June 2019 to October 2021 were selected as research objects.The expression level of FOXA2 protein in tumor and adjacent tissues was analyzed by Western blotting.The control plasmid and FOXA2 overexpression plasmid were transfected into human ovarian cancer cell SKOV3 with transfection reagents,which were respectively the control group and the observation group.The ability of migration,invasion and epithelial mesenchymal transformation in the control group and the observation group was analyzed by scratch test,Transwell and Western blotting.The migration ability of cells was analyzed by tumor transplantation experiment in vitro.The expression of FOXA2 target gene was analyzed by fluorescent quantitative polymerase chain reaction(PCR).T-test was used to compare the data between groups.Results The expression level of FOXA2 protein in para-cancerous tissues(1.13±0.24)was significantly higher than that in ovarian cancer tissues(0.47±0.14,t=18.640,P<0.05).The rate of cell wound healing in the control group[(83.67±9.95)%]was significantly higher than that in the observation group[(56.60±7.06)%,t=5.452,P<0.05].The number of invasive cells in the control group[(150.83±18.35)]was significantly greater than that in the observation group[(84.50±8.89),t=7.970,P<0.05].The level of E-cadherin protein expression in the control group(0.74±0.12)was significantly lower than that in the observation group(1.03±0.16,t=3.626,P<0.05).The expression levels of the interstitial markers(Snail and N-cadherin protein)in the control group(1.16±0.12,1.30±0.11)were significantly higher than those in the observation group(0.66±0.08,0.76±0.06,t=8.305,10.300,P<0.05).The number of lymph node metastasis in the control group(9.38±1.69)was significantly greater than that in the observation group(3.13±1.46,t=7.934,P<0.05).The expression level ofβ-catenin and c-Myc mRNA in the control group(1.10±0.12,1.23±0.11)was significantly higher than that in the observation group(0.79±0.08,0.82±0.08,t=5.398,7.305,P<0.05).Conclusion FOXA2 that is down-regulated in ovarian cancer involved in the migration,invasion and epithelial mesenchymal transformation of ovarian cancer cells by the expression ofβ-catenin and c-Myc.
作者 任璐 曹芹雪 王宁 Ren Lu;Cao Qinxue;Wang Ning(Department of Gynecology,Huaihe Hospital of Henan University,Kaifeng 475004,China)
出处 《中华实验外科杂志》 CAS 北大核心 2023年第4期712-715,共4页 Chinese Journal of Experimental Surgery
关键词 叉头框蛋白A2 卵巢癌 迁移 侵袭 上皮-间充质转化 Forkhead box protein A2 Ovarian cancer Migration Invasion Epithelial mesenchymal transformation
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