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人乳头瘤病毒16 E6蛋白通过Wnt/β-catenin通路促进食管癌Eca109细胞增殖、迁移的实验研究 被引量:5

E6 Protein from HPV16 Promotes the Proliferation and Migration of Esophageal Cancer Eca109 Cells via the Wnt/β-catenin Pathway
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摘要 人乳头瘤病毒16(Human papillomavirus 16,HPV16)感染与食管癌的发生密切相关,HPV16编码的HPV16E6蛋白是主要的致癌蛋白,已经在宫颈癌细胞中被证实能够促进癌细胞的增殖、迁移,同时也可激活Wnt/β-catenin通路。但HPV16 E6蛋白对食管癌细胞增殖、迁移的调控作用及机制尚未阐明。为研究HPV16 E6蛋白对食管癌Eca109细胞增殖、迁移及细胞中Wnt/β-catenin通路的调节作用,本研究培养食管癌Eca109细胞并分组,空白对照组用不含药物及质粒的DMEM处理,空白pcDNA3.1组转染空白的pcDNA3.1质粒,HPV16 E6组转染HPV16 E6基因的pcDNA3.1质粒,HPV16 E6+XAV组转染HPV16 E6基因的pcDNA3.1质粒、同时加入β-catenin抑制剂XAV939;并检测细胞的增殖、迁移活力及细胞中增殖基因、迁移基因、Wnt/β-catenin通路基因的表达。结果显示,转染24h后,HPV16 E6组细胞的增殖活力、迁移活力以及细胞中c-myc、cyclinD1、bcl-2、HMGA-2、N-cadherin、Wnt2、β-catenin的蛋白表达量均明显高于空白对照组、空白pcDNA3.1组;HPV16 E6+XAV组细胞的增殖活力、迁移活力以及细胞中c-myc、cyclinD1、bcl-2、HMGA-2、N-cadherin、β-catenin的蛋白表达量均明显低于HPV16 E6组,Wnt2的蛋白表达量与HPV16 E6组比较无明显差异。本研究揭示,HPV16 E6蛋白能够促进食管癌Eca109细胞的增殖、迁移且该作用与激活Wnt/β-catenin通路有关。 Human papillomavirus 16(HPV16)infection is closely related to esophageal cancer. The E6 protein encoded by HPV16 has been shown to promote the proliferation and migration of cervical cancer cells,and also to activate the Wnt/β-catenin pathway. However,the regulatory effect and mechanism of action of HPV16 E6 protein on the proliferation and migration of esophageal cancer cells have not been elucidated. We wished to study the effects of HPV16 E6 protein on the proliferation,migration and Wnt/β-catenin pathway of esophageal cancer(Eca109) cells. Eca109 cells were cultured and grouped. The blank control group was treated with Dulbecco’s modified Eagle’s medium without drugs or plasmids. The blank pcDNA3.1 group was transfected with blank pcDNA 3.1 plasmid. The HPV16 E6 group was transfected with HPV16 E6 gene pcDNA 3.1 plasmid. The HPV16 E6+XAV group was transfected with HPV16 E6 gene pcDNA 3.1 plasmid,and a β-catenin inhibitor(XAV939)added. Cell proliferation,migration activity as well as expression of proliferation-,migration-and Wnt/β-catenin pathway-associated genes were measured. Results showed that twenty-four hours after transfection,the proliferation and migration of cells as well as protein expression of c-myc,cyclin D1,bcell lymphoma(bcl)-2,high mobility group-AT-hook(HMGA)-2,N-cadherin,Wnt2 and β-catenin in cells of the HPV16 E6 group were significantly higher than those in the blank control group and the blank pDNA3.1 group. The proliferation and migration of cells and protein expression of c-myc,cyclin D1,bcl-2,HMGA-2,Ncadherin,Wnt2 and β-catenin in cells of the HPV16 E6+XAV group were significantly lower than those of the HPV16 E6 group,whereas the protein expression of Wnt2 showed no significant difference with that of the HPV16 E6 group. The present study suggested that HPV16 E6 protein can promote the proliferation and migration of Eca109 cells,and this effect is related to activation of the Wnt/β-catenin pathway.
作者 黄毓娟 沈舒文 惠建平 宋健 郑星 HUANG Yujuan;SHEN Shuwen;HUI Jianping;SONG Jian;ZHENG Xing(Basic Medical College,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Department of Traditional Chinese Medicine,First Clinical Medical College,Shaanjci University of Traditional Chinese Medicine,Xianyang 712046,China;Department of Gastroenterology,Affiliated Hospital of Shaanjci University of Traditional Chinese Medicine,Xianyang 712046,China)
出处 《病毒学报》 CAS CSCD 北大核心 2020年第2期255-261,共7页 Chinese Journal of Virology
基金 陕西省教育厅立项资助项目(项目号:17JK0219),题目:基于血清胃泌素-17水平的金果胃康胶囊干预上皮内瘤变中医高危证型的效应研究 全国名老中医药专家沈舒文传承工作室建设项目(国中医药人教发【2016】42) 陕西省教育厅立项资助项目(项目号:18JK0225),题目:基于Wnt/Lgr5信号通路调控探讨金果胃康胶囊对慢性萎缩性胃炎癌前病变干预的分子机制。
关键词 食管癌 人乳头瘤病毒16(HPV16) 增殖 迁移 Esophageal cancer Human papillomavirus 16(HPV16) Proliferation Migration
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