基于“肺肾相关”从性激素及其受体和EGFR交叉信号通路探讨肾虚内环境对非小细胞肺癌的影响及机制

项目名称： 基于“肺肾相关”从性激素及其受体和EGFR交叉信号通路探讨肾虚内环境对非小细胞肺癌的影响及机制

项目编号： No.81473497

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王淑玲

作者单位： 郑州大学

项目金额： 75万元

中文摘要： 本研究首先比较去势肾虚小鼠和正常小鼠Lewis肺癌移植瘤和转移瘤的差异探讨肾虚内环境对肺癌形成有无影响；其次用四诊和调查问卷的方法探讨NSCLC患者肾虚程度、肾虚类型与肺癌临床特征和预后的关系；第三，以性激素及其受体和EGFR交叉通路为切入点，采用RT-PCR、Western blot等实验技术，观察不同水平E2、T对小鼠Lewis肺癌移植瘤和转移瘤的影响及性别差异，探讨E2、T对其受体ERα、ERβ、AR表达的调控，分析E2、T与其受体、EGFR及下游信号PI3K-AKT等的相关性；利用RNA干扰技术分别特异性抑制肺腺癌A549细胞中ER和AR的表达，观察癌细胞增殖侵袭和转移的变化，用real time-PCR、等检测EGFR及相关信号分子的表达；初步揭示肾虚内环境影响肺癌的机制，为肾虚内环境是肺癌发生发展的内因之一的假说和从肾论治肺癌及靶向药物的研发和应用提供依据。

中文关键词： 非小细胞肺癌；肾虚内环境；性激素及其受体；表皮生长因子受体；交叉信号通路

英文摘要： Firstly, this study compared the differences between transplanted Lewis lung tumors and metastases in castrated mice of deficiency of kidney and normal mice in order to investigate whether environment of deficiency of kidney could influence on the formation of lung cancer . secondly four diagnostic methods and questionnaire was used to explore the extent , the types , clinical characteristics(TNM staging, histological type, degree of differentiation) and prognosis of NSCLC of deficiency of kidney. Thirdly, with sex hormone , its receptors as well as EGFR pathway as a starting point, RT-PCR，Western blot and other experimental techniques were used to observe the effects and gender differences that different levels of E2, T affected on xenografted tumor of Lewis lung carcinoma and metastatic tumor; to discuss that E2, T regulated expression of its receptors ERα, ERβ, AR; to analysis the correlation between E2, T ,its receptor, EGFR and downstream signal PI3K-AKT.Finally RNA interference techniques were used to specifically inhibit the expression of ER and AR of lung adenocarcinoma A549 cells ,then characteristics change of the invasion and metastasis of cancer cells were observed ,expression of EGFR and related signaling molecules were detected with real time-PCR, Western blot. The study initially revealed the mechanisms that the environment of deficiency of kidney worked on lung cancer, which also provided the basis for the hypothesis the environment of deficiency of kidney is one of the internal reasons of development of lung cancer, from the kidney Treating lung cancer as well as targeted drug development and application.

英文关键词： non-small cell lung cancer;NSCLC;the kidney dificiency internal environment;the sex hormone and its receptor;epidermal growth factor receptor;EGFR;cross signal pathway