调控miR-101/VEGF-C通路抑制膀胱癌淋巴道转移与降低化疗耐药的双重作用研究

项目名称： 调控miR-101/VEGF-C通路抑制膀胱癌淋巴道转移与降低化疗耐药的双重作用研究

项目编号： No.81202005

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： 陈敏丰

作者单位： 中南大学

项目金额： 23万元

中文摘要： 晚期膀胱癌治疗棘手，究其原因主要在于:肿瘤向深部浸润和远处转移、化疗耐药。同时解决这两个问题，则膀胱癌的治疗水平将会明显提高。申请人所在的课题组前期国家自然科学基金课题（30700832）研究提示VEGF-C促进了膀胱癌细胞的淋巴道转移，且抑制丝裂霉素诱导膀胱癌细胞的凋亡；同时，另一省自然科学基金重点项目课题研究显示miR-101在膀胱癌中调控VEGF-C的表达。那么，我们设想：调控miR-101/VEGF-C通路是否可以同时抑制膀胱癌淋巴道转移与降低化疗耐药性呢？本课题拟先进行细胞实验，然后深入到动物实验，临床病例分析，多个角度进行深入研究，以期明确升高miR-101的表达是否可以抑制VEGF-C，是否可达到同时降低膀胱癌的浸润转移能力和化疗耐药性的目的。其结果有望深入认识miRNA在膀胱癌淋巴道转移过程中的作用，并为控制膀胱癌侵袭转移、化疗增敏提供新的靶点。

中文关键词： 膀胱癌；MiR-101；VEGF-C；化疗耐药；转移

英文摘要： Bladder cancer of advanced-stage is lack of effective treating method. There are two main reasons. One is the invasion and metastasis of tumor; the other one is the chemotherapy resistance. It will be an important milestone of the treatment for bladder cancer, if these two problems could be solved simultaneously. Our former research of ESS(30700832） shows that VEGF-C could promote the lymphatic metastasis of bladder cancer and inhibit the apoptosis of cancer cells induced by mitomycin;meanwhile，another research of HNNSF shows that mir-101 regulats expression of VEGF-C in bladder cancer.We assume that it is possible to inhibit lymphatic metastasis and reduce chemotherapy resistance of bladder cancer at the same time by regulating the pathway of mir-101/VEGF-C.The purpose of this topic is to find out whether the up-regulated expression of mir-101 could inhibit the expression of VEGF-C,and then reduce the ability of invasion and metastasis of bladder cancer as well as the chemotherapy resistance,through cell experiment , animal experiment and clinical case analysis. We are about to realize more about the function of miRNA in the process of lymphatic metastasis of bladder cancer,and furtherly provide potential new target for the control of bladder cancer cell invasion and metastasis and the chemotherapeutic sensiti

英文关键词： bladder cancer；miR-101；;Vascular Endothelial Growth-C；chemotherapy resistance；metastasis