糖皮质激素受体在膀胱癌进展中的作用及其机制研究

项目名称： 糖皮质激素受体在膀胱癌进展中的作用及其机制研究

项目编号： No.81202022

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 郑一春

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 膀胱癌是最常见的泌尿系统恶性肿瘤，并且其发病仍呈逐年上升趋势。浸润性膀胱癌，手术联合常规放、化疗预后不佳，有探索新治疗方法的临床需要。糖皮质激素受体(GR)活化可导致多种肿瘤细胞生长停滞并诱导凋亡。我们前期研究发现糖皮质激素受体在膀胱癌100%表达，其表达水平与肿瘤恶性程度、预后相关。体外实验初期结果表明糖皮质激素作用可导致膀胱癌细胞生长减缓。本研究拟通过对临床标本检测，了解膀胱癌中GR的表达及其与肿瘤分级、分期、转移、预后的相关性。利用shRNA基因封闭技术研究GR低表达膀胱癌细胞株与其父系GR高表达膀胱癌细胞株之间体外培养条件下生长、侵袭能力的变化与分子机制。建立SCID小鼠荷瘤模型，观察不同克隆细胞药物作用下成瘤和侵袭、转移情况。测定临床正常对照与膀胱癌患者血液标本中血皮质醇浓度，分析血皮质醇水平与膀胱癌发病、临床分级、分期和预后的相关性。

中文关键词： 糖皮质激素受体；膀胱癌；地塞米松；Compound A；侵袭

英文摘要： Bladder cancer is the most common urinary malignant tumor with rising incidence . The prognosis is really poor for patients with invasive bladder cancer; even they are received treatment combined with surgical operation, chemotherapy and radiotherapy. Activation of glucocorticoid receptor (GR) can lead to growth arrest and apoptosis in tumors. Our previous study found that the positivity of GR expression in bladder cancer is 100%. The expression level of GR was related to grade, stage, and prognosis. Preliminary in vitro study showed that the glucocorticoid could inhibit the growth of bladder cancer cell. Our proposal is to analyze 120 clinical specimens of bladder cancer, study the relationship between GR expression and tumor grade, stage, metastasis, and prognosis. GR negative cell lines will be established by using lentiviri burdening GR-shRNA. We will compare cell growth, apoptosis, morphology, invasion and angiogenesis between parental cells and GR knock-down cells, under different invention, and the molecular mechanisms will be investigated. SCID mice tumor-bearing model will be brought out to observe the effect of dexamethasone on tumorigenesis, invasion and metastasis in different cell clones. Serum cortisol concentration will be evaluated in patients of bladder cancer and healthy adults. Analysis will b

英文关键词： glucocorticoid receptor；bladder cancer；Dexamethasone；Compound A；invasion