浸润性膀胱癌是危及人类健康的重大疾病，发病机制不详，预后差。30%的浸润性膀胱癌患者确诊时出现镜下转移，超过90%的患者最终死于肿瘤转移。有研究表明，浸润性膀胱癌的侵袭、转移与代谢通路改变密切相关。我们前期蛋白质组学研究中亦发现浸润性膀胱癌及其间质中均发生了显著代谢改变，即膀胱癌细胞中的氧化磷酸化改变与癌间质细胞中的有氧酵解改变。我们推测膀胱癌间质成分通过有氧酵解以及营养素定向转运饲育膀胱癌细胞氧化磷酸化，从而形成代谢偶联。因此本课题正是着眼于膀胱癌代谢改变，进一步通过体内外实验观察共生环境下膀胱癌细胞及间质细胞的衍生变化，从氧化应激、DNA损伤、自体吞噬、糖酵解、线粒体功能等多方面为代谢偶联提供佐证，并利用联合靶向性小干扰RNA技术阻断定向转运通路导致代谢脱偶联，探讨其体内外抗增殖及侵袭作用，为阐明膀胱癌的分子发病机制及其靶向治疗夯实理论基础。

Muscle-invasive bladder cancer is one of the serious diseases threatening the health of humans. Till now, the prognosis of bladder cancer is still poor out of the unclear molecular mechanism. 30% of the patients demonstrate microscopic evidence of metastasis at the time of diagnosis and 90% of the patients died of metastasis at last. Studies have shown that the invasion and metastasis of muscle-invasive bladder cancer intimately related to metabolic pathways. Our previous proteomic studies had discovered that both cancer cells themselves and corresponding stromal cells exist significantly metabolic changes. Namely, significant tendencey of oxidative phosphorylation in cancer cells and significant tendencey of glycolysis in stromal cells. Based on our findings, we deduce that the stromal cells undergo aerobic glycolysis and produce the energy-rich metabolites.Meanwhile,these metabolites transferred to cancer cells, where they enter oxidative phosphorylation. Thus a metabolic-coupling is constructed. The present research item is just focus on the metabolic changes in muscle-invaisve bladder cancer, and furthe to observe the deriveing changes in cancer cells and stromal cells in a prerequisite of co-culture. All the scientistic contents are under the circumstance of offer evidences to metabolic-coupling and mainly include oxidative stress, DNA damage, autophagy, glycolysis, mitochondrial function, etc. Furthermore, combined target small interfering technique is performed to block energy transfer and thus to produce artificial metabolic-uncoupling. The successor of combined target treatment is investigated by in vitro and in vivo experiments. Above all things, present research item will help to explain the mechanism of bladder cancer and lay the foundation to novel targeted antitumor therapy.