食管癌相关基因4通过p53通路诱导食管癌细胞G1期阻滞

Esophageal cancer related gene 4 induced block of esophageal cancer cells in G1 phase by p53 pathway

目的 探讨食管癌相关基因4（ECRG4）在食管癌中的抑癌功能及其机制.方法 构建ECRG4基因表达质粒pcDNA3.1-ECRG4,筛选ECRG4稳定转染细胞株.通过细胞增殖曲线和裸鼠移植瘤实验检测ECRG4过表达对食管癌细胞体外增殖和体内裸鼠成瘤能力的影响;流式细胞仪检测ECRG4过表达对食管癌细胞细胞周期的影响;Western blot检测食管癌细胞中ECRG4过表达,细胞周期调控基因p53和p21蛋白表达的变化.结果 ECRG4基因过表达,食管癌细胞体外增殖和体内裸鼠移植瘤生长减缓,体内肿瘤生长抑制率为48.5％,和空载质粒对照组比较,差异有统计学意义（P ＜0.05）;ECRG4基因过表达诱导食管癌细胞细胞周期G1期阻滞,和空载质粒对照组比较,差异有统计学意义（P＜0.05）;ECRG4基因过表达,导致食管癌细胞中p53和p21蛋白表达增加,与空载质粒对照组比较,差异有统计学意义（P＜0.05）.结论 ECRG4通过p53通路诱导食管癌细胞细胞周期G1期阻滞.

Objective To investigate the tumor-suppressing function and mechanism of esophageal cancer related gene 4 （ECRG4） in esophageal carcinoma.Methods The ECRG4 gene expression plasmid pcDNA3.1-ECRG4 was constructed,and the EC9706 cell line with ECRG4 gene stable transfection was achieved.The effect of ECRG4 gene over-expression on esophageal cancer cells proliferation in vitro and tumor growth in vivo was studied by cell growth curves and tumor formation in nude mice experiments.The cell cycle change was examined by flow cytometry.The cell cycle regulation genes p53 and p21 protein expression changes were detected by Western blotting.Results The esophageal cancer cells proliferation in vitro and tumor growth in vivowere decreased in ECRG4 over-expression group,and the in vivo tumor growth inhibition rate was 48.5%,as compared with empty plasmid control group （P 〈 0.05）.ECRG4 over-expression induced block of esophageal cancer cells in G1 phase as compared with empty plasmid control group （P 〈 0.05）.The p53 and p21 protein expression was increased in ECRG4 over-expression group as compared with empty plasmid control group （P 〈 0.05）.Conclusion ECRG4 induced block of esophageal cancer cells in G1 phase by p53 pathway.