低氧条件下食管癌细胞中PRRX1通过p53介导线粒体通路诱导细胞凋亡的研究  

PRRX1 induces apoptosis through p53-mediated mitochondrial pathway in esophageal cancer cells under hypoxia

作　　者：王珍[1] 章恒[1] 张建庆[1] 古丽娜尔·吐尔地[1] WANG Zhen;ZHANG Heng;ZHANG Jianqing;Gulinal·Turdi(Radiotherapy Center,People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院放疗中心,新疆乌鲁木齐830000

出　　处：《现代肿瘤医学》2021年第24期4292-4298,共7页Journal of Modern Oncology

基　　金：新疆维吾尔自治区自然科学基金项目(编号:2019D01C108)。

摘　　要：目的:探究低氧条件下配对相关同源框1(PRRX1)通过p53介导的线粒体通路诱导食管癌细胞凋亡。方法:GEPIA2数据库分析PRRX1基因在食管癌组织和正常食管组织中的表达变化。RT-qPCR和Western blotting分别检测HEEC、Eca-109、TE-1细胞中PRRX1的mRNA和蛋白表达。二氧化钴处理模拟低氧微环境,在常氧和低氧条件下检测Eca-109、TE-1细胞中PRRX1的mRNA和蛋白表达情况。采用小干扰RNA(Si-PRRX1)转染TE-1细胞,设置分组为Hypoxia-Si-NC、Hypoxia-Si-PRRX1。流式细胞术检测TE-1细胞凋亡,RT-qPCR检测p53 mRNA表达,Western blotting检测p53、BCL-2、BAX、Cleaved-Caspase3等蛋白表达,在TE-1-PRRX1 KO细胞系中过表达p53,检测BCL-2、BAX、Cleaved-Caspase3等蛋白表达。结果:PRRX1在食管癌组织及细胞系中均高表达。在TE-1细胞中敲低PRRX1,抑制细胞凋亡,下调p53的mRNA及蛋白表达,抑制BAX、Cleaved-Caspase3蛋白表达,促进BCL-2蛋白表达;过表达PRRX1则上调p53蛋白表达。在TE-1-PRRX1 KO细胞系中过表达p53显著抑制BCL-2蛋白表达,促进BAX、Cleaved-Caspase3蛋白表达。结论:低氧条件下,PRRX1通过p53介导的线粒体通路诱导食管癌细胞凋亡。Objective:To explore the study of PRRX1 inducing apoptosis of esophageal cancer cells through p53-mediated mitochondrial pathway under hypoxia.Methods:GEPIA2 database was used to analyze the gene expression of PRRX1 in esophageal cancer tissue and normal esophageal tissue.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of PRRX1 in HEEC,Eca-109 and TE-1 cell lines,respectively.Cobalt dioxide treatment simulated the hypoxic microenvironment.The mRNA and protein expression level of PRRX1 in Eca-109 and TE-1 cells was detected under normoxia and hypoxia conditions.TE-1 cells were transfected with small interfering RNA(Si-PRRX1)and grouped into Hypoxia-Si-NC and Hypoxia-Si-PRRX1.The apoptosis rate of TE-1 cells was detected by flow cytometry.The mRNA expression of p53 was detected by RT-qPCR,and the proteinexpression of p53,BCL-2,BAX,Cleaved-Caspase3 was detected by Western blotting.TE-1-PRRX1 KO cell linewas constructed,and the protein expression of BCL-2,BAX,Cleaved-Caspase3 were detected after overexpressionof p53.Results:PRRX1 was highly expressed in both esophageal cancer tissue and cell lines.Knockdown of PRRX1 in TE-1 cells inhibited cell apoptosis,down-regulated p53 mRNA and protein expression,inhibited protein expres-sion of BAX and Cleaved-Caspase3,and promoted BCL-2 protein expression.Overexpression of PRRX1 up-regu-lated p53 protein expression.Overexpression of p53 in TE-1-PRRX1 KO cell line significantly inhibited BCL-2 protein expression,while promoted BAX and Cleaved-Caspase3 protein expression.Conclusion:PRRX1 induces ap-optosis of esophageal cancer cells through p53-mediated mitochondrial pathway under hypoxia.

关 键 词：食管癌 低氧 PRRX1 P53 线粒体 凋亡 

分 类 号：R735.1[医药卫生—肿瘤]