OPN基因与食管癌浸润及青蒿琥酯抑制食管癌细胞生长的关系研究  

Relationship between OPN gene expression, esophageal cancer metastasis and the growth inhibition effect of artesunate on esophageal cancer cells

作　　者：刘亮[1] 王莉[1] 杨祺[1] 左连富[1] 

机构地区：[1]河北医科大学第四医院肿瘤研究所流式细胞室,石家庄050011

出　　处：《解放军医学杂志》2017年第1期23-28,共6页Medical Journal of Chinese People's Liberation Army

基　　金：河北省医学科学研究重点课题(20160167;20150345);河北省普通高等学校强势特色学科肿瘤学建设([2005]52)~~

摘　　要：目的探讨骨桥蛋白(OPN)基因与食管癌发生及浸润转移的关系,以及青蒿琥酯(Art)抑制食管癌细胞生长的作用与OPN蛋白表达的关系。方法应用原位杂交及免疫组织化学方法检测45例食管鳞癌组织、21例不典型增生组织、24例正常的食管黏膜上皮组织中OPN基因及蛋白的表达,并分析其与食管癌临床病理特征的关系。以不同浓度(0、30、60、120μmol/L)青蒿琥酯干预食管鳞癌Eca109细胞24h,采用流式细胞术检测细胞周期及细胞中OPN蛋白的表达水平。结果 OPN基因及蛋白在食管鳞癌组织中的表达水平显著高于不典型增生及正常组织(P<0.01),且不典型增生组织中的表达水平显著高于正常组织(P<0.05)。OPN基因及蛋白在食管鳞癌组织中的表达与淋巴结转移及浸润深度呈正相关(P<0.05),与患者性别、年龄及肿瘤的分化程度无明显相关(P>0.05)。青蒿琥酯作用24h后,Eca109细胞增殖指数及OPN蛋白表达水平均显著降低(P<0.01),且具有浓度依赖性。结论 OPN基因在食管鳞癌组织中异常高表达,可能参与了食管癌的发生及浸润转移。青蒿琥酯抑制食管癌细胞生长的作用可能与其下调细胞中OPN蛋白的表达有关。Objective To study the relationship between osteopontin（OPN） gene expression and the development and metastasis of esophageal cancer, and explore the effect of growth inhibitory of artesunate（Art） on regulating the expression of OPN in esophageal carcinoma cells. Methods The expressions of OPN gene and protein were detected in normal esophageal tissue（24 cases）, esophageal dysplasia（21 cases） and esophageal squamous cell carcinoma（ESCC） tissue（45 cases） by in situ hybridization and immunohistochemistry, and the relationships between the OPN gene and protein expressions and the pathological features were analyzed with SAS software. After intervention with different concentrations of Art（0, 30, 60, 120mol/L） on ESCC Eca109 cells for 24 h, the levels of OPN expression and cell cycle were detected by flow cytometry. Results The expression levels of OPN gene and protein were significantly higher in esophageal cancer tissues than in esophageal dysplasia and normal esophageal tissue（ P〈0.01）, and in esophageal dysplasia than in normal esophageal tissue（P〈0.05）. The expression levels of OPN gene and protein in esophageal cancer tissues showed no relations with patients＇ gender, age and the degree of tumor differentiation（P〉0.05）, but showed a positive correlation with lymph node metastasis and the invasion depth of esophageal cancer（P〈0.05）. After treatment by Art for 24 h, the proliferation index of Eca109 cells and the expression of OPN protein decreased significantly（P〈0.01） in a concentration dependent manner. Conclusions The abnormal high expression of OPN gene may participate in the occurrence, invasion and metastasis of esophageal cancer, so can be used as an objective index of metastasis for esophageal cancer. Art inhibits the growth of esophageal carcinoma cells by down-regulating the expression of OPN protein.

关 键 词：食管肿瘤 骨桥蛋白质 肿瘤转移 细胞增殖 

分 类 号：R735.1[医药卫生—肿瘤]