腺苷酸活化蛋白激酶促进MET过程对胃癌细胞增殖和侵袭力的影响及机制研究

项目名称： 腺苷酸活化蛋白激酶促进MET过程对胃癌细胞增殖和侵袭力的影响及机制研究

项目编号： No.81460370

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张飞雄

作者单位： 宁夏医科大学

项目金额： 47万元

中文摘要： 最近的研究发现腺苷酸活化蛋白激酶(AMPK)与消化系肿瘤细胞的生长、增殖、凋亡及侵袭转移等过程密切相关。我们前期的工作发现AMPK激活激活剂增加上皮细胞间连接形成，促进MET过程；同时人高分化胃腺癌组织AMPK呈腔缘型膜定位高表达模式，与HIF-1α表达呈负相关，结果提示AMPK 存在对肿瘤细胞MET过程的调控并对肿瘤生物学行为产生潜在影响，目前其具体分子机制还不清楚。本课题利用人胃癌细胞的体外培养，通过AMPK激活剂及抑制剂处理，建立AMPK基因敲减及过表达人胃癌细胞模型，检测胃癌细胞的增殖和侵袭能力，进一步检测AMPK上游激酶LKB1以及其下游MET相关分子的表达，并结合人胃癌组织AMPK表达的临床病理分析工作，旨在明确AMPK促进 MET过程对胃癌细胞增殖和侵袭能力的潜在抑制性作用及其机制，为胃癌的临床诊断和治疗提供潜在的新靶点，为相关药的抗肿瘤治疗研究提供实验依据。

中文关键词： C07_胃肿瘤；腺苷酸活化蛋白激酶；间质上皮转化；增殖；侵袭力

英文摘要： Adenosine monophosphate activated protein kinase (AMPK) is closely related with tumor cell growth, proliferation, apoptosis and metastasis of digestive system. Our previous work found that AMPK activation of activator increased the cell junction formation of the epithelial cells and promoted the mesenchymal-epithelial transition(MET) process of such the cells;The IHC staining results was showed a membrane and luminal type with high expression patterns of AMPK in highly differentiated gastric adenocarcinoma tissues and negatively correlated with the expression of HIF-1 α.These results suggest that AMPK play a key role in regulation of MET process of the tumor cells and has a potential impact on biological behavior of tumor.For now the detailed molecular mechanism is not clear. In this study,we use the human gastric cancer cells in vitro model, use activator and inhibitor of AMPK, and establish the AMPK gene knockdown and overexpression cell model of human gastric cancer, to detect the proliferation of gastric cancer cells and the invasive ability, and further to detect the expression of AMPK/LKB1 kinase and its downstream MET related molecules, and combine with the expression of AMPK for the clinical and pathological analysis of human gastric cancer. To investigate the potential and mechanism of AMPK promoting MET process and its inhibitory effect on invasion and proliferation of gastric cancer cells.The further study provides a potential new target for clinical diagnosis and treatment of gastric cancer, and provides the experimental basis for the anti tumor treatment medicine.

英文关键词： gastric cancer;AMP-activated protein kinas;mesenchymal-epithelial transition;proliferation;invasiveness