膜联蛋白A1在食管癌组织的表达及其临床意义

Expression of annexin A1 protein in esophageal carcinoma and its clinical significance

目的 探讨膜联蛋白A1（Annexin A1）在食管癌发生和发展过程中的生物学作用.方法 采用免疫组织化学分析94例食管鳞状细胞癌组织和周围正常组织中Annexin A1蛋白的表达.采用Annexin A1过表达和敲低慢病毒感染人永生化食管上皮细胞株SHEE,得到稳定细胞株.采用细胞计数试剂盒（CCK-8）分析Annexin A1过表达和敲低细胞株细胞增殖能力;采用Transwell法分析Annexin A1过表达和敲低细胞株细胞侵袭能力;采用软琼脂法分析细胞克隆形成能力;采用体内细胞移植实验分析Annexin A1过表达细胞株在体内形成肿瘤能力.结果 与正常食管组织比较,食管癌组织中Annexin A1蛋白表达水平明显增加（P=0.004）.与对照细胞株比较,Annexin A1过表达细胞株细胞增殖能力（P=0.026）和侵袭（P=0.017）能力明显增加,而Annexin A1敲低的细胞株,细胞增殖能力（P=0.019）和侵袭能力（P=0.023）明显下降.与对照细胞株比较,Annexin A1过表达细胞株克隆形成能力明显增强（P=0.022）,而Annexin A1敲低细胞株克隆形成能力明显下降（P=0.035）.体内成瘤实验显示,与对照细胞株比较,Annexin A1过表达细胞株体内肿瘤形成率明显增加（P=0.001）.结论 Annexin A1蛋白在食管癌组织中呈过表达,其参与了食管癌细胞的生长、侵袭和肿瘤形成.

Objective To investigate the biological role of Annexin A1 protein in carcinogenesis and progression of esophageal carcinoma.Methods Annexin A1 protein level was analyzed by immunohistochemical assay in 94 cases of esophageal squamous carcinoma tissues and surrounding normal tissues.Annexin A1 overexpression and knockdown stable cell lines in human immortalized esophageal epithelial cell line SHEE were constructed by lentivirus.Cell proliferation of Annexin A1 overexpression and knockdown stable cell lines were analyzed by cell counting kit-8 （CCK-8）.Cell invasion ability of Annexin A1 overexpression and knockdown stable cell lines were analyzed by transwell method.Cell colony forming ability in stable cell lines was analyzed by soft agar assay.Tumor formation in mice was analyzed by cell transplantation.Results Compared with the normal esophageal tissues,the expression levels of Annexin A1 protein in esophageal cancer tissues increased significantly （P=0.004）.Compared with the control cell lines,proliferation （P=0.026） and invasion （P=0.017） ability in Annexin A1 protein overexpression cell lines significantly increased,while in the Annexin A1 protein knockdown cell lines,cell proliferation （P=0.019） and invasion （P=0.023） ability significantly decreased.Compared with the control cell lines,the clonal formation ability of Annexin A1 overexpression cell lines significantly enhanced（P=0.022）,while the ability of clones formation in Annexin A1 protein knockdown cell line significantly decreased （P=0.035）.In vivo tumor formation test showed that the tumor formation rate in Annexin A1 protein overexpressing cell lines significantly increased compared with control cell lines （P=0.001）.Conclusion Annexin A1 protein overexpressed in esophageal carcinoma tissues,which was involved in the growth,invasion and tumorigenesis of esophageal cancer cells.