健脾解毒方对COX-2激活JNK信号通路介导大肠癌多药耐药的调控研究

项目名称： 健脾解毒方对COX-2激活JNK信号通路介导大肠癌多药耐药的调控研究

项目编号： No.81202812

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 隋华

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 多药耐药（MDR）是影响结直肠癌临床化疗疗效的重要因素之一，但诱发多药耐药的机制原理尚不清楚。前期研究发现COX-2通过激活JNK信号通路介导MDR1/P-gp的过表达，是引起多药耐药的重要诱因。同时临床用药也证实健脾解毒中药复方能够通过抑制P-gp的表达逆转肠癌耐药，但具体作用靶点仍未明确。因此本研究构建COX-2过表达和siRNA干扰慢病毒载体，采用分子克隆，基因沉默，Real-time PCR, Western blot等技术，针对结肠癌耐奥沙利铂现象，进行体内体外研究，探讨健脾解毒中药对COX-2/JNK信号传递介导的结直肠癌多药耐药的调控机制。这对于进一步完善诱导多药耐药发生的信号转导途径，明确中药防治肿瘤多药耐药的作用靶点，具有重要意义。

中文关键词： 大肠癌；多药耐药；COX-2；JNK；中药复方

英文摘要： The clinical use of chemotherapeutic drugs in colorectal cancer treatment is limited by the occurrence of multidrug resistance (MDR). However, the underlying mechanism remains unknown. Our previous studies showed that COX-2 induced up-regulation of MDR1/P-gp, which was associated with an enhanced activity of JNK signal transduction. Clinical practice have proved that Jian-Pi-Jie-Du herbal formula reversed drug-resistance in colorectal cancer, but the target is still unclear. In this study, we built COX-2 recombinant lentivirus by overexpression and RNAi. Molecular cloning, siRNA, Real-time PCR, Western blot and other experimental techniques will be used to explore the mechanism of drug-resistance aroused by oxaliplatin in vitro and in vivo, as well as to investigate the effects of Jian-Pi-Jie-Du herbs on COX-2/JNK signaling in colorectal cancer. It will be helpful to find the target in the prevention and treatment of drug-resistance tumor.

英文关键词： colorectal cancer；multidrug resistance；COX-2；JNK；Chinese herbal formal