抗EPOR抗体在肾细胞癌中的治疗作用

肾细胞癌是泌尿系统中常见的恶性肿瘤之一，目前晚期肾细胞癌的治疗以针对血管生成的靶向药物治疗为主，但尚存在不良反应较重及用药后一段时间后出现耐药等问题，临床中迫切需要新的有效治疗方法。EPO-EPOR通路是抑癌基因VHL调控的下游信号通路之一，我们前期研究结果发现EPO及EPOR在肾细胞癌中存在共表达现象且在肾细胞癌发病机制中起重要作用，进一步研究发现此通路可能成为治疗肾细胞癌的新靶点。我们拟利用自己研发的抗EPOR多克隆抗体，研究其与不同类型肾癌细胞的结合能力及对肾肿瘤细胞EPO-EPOR通路活性的影响，在体内外观察肿瘤生长曲线，明确其对肾细胞癌增殖、凋亡及侵袭能力的影响。并进一步探究抗EPOR抗体与现有的靶向药物联合使用是否具有协同治疗肾细胞癌的作用。本项研究探索抗EPOR抗体在肾细胞癌中的治疗作用，将明确其是否可能成为治疗肾细胞的新型靶向药物，为临床中治疗肾细胞癌提供新依据。

Renal cell carcinoma (RCC) is one of the most common neoplasms in urology, and targeted therapy targeting angiogenesis is an important treatment for metastatic RCC (mRCC). However, currently most of the patients will have severe side effects and will gain drug resistance after a period of targeted therapy, so it is very important to find out some new targeted drugs for mRCC. EPO-EPOR pathway is downstairs tumor suppressor gene VHL, our previous work confirmed the co-expression of EPO and EPOR in RCCs, this pathway plays an important role in the tumorigenesis of RCC, down-regulation of EPOR expression in RCC cells resulted in inhibition of growth and invasiveness in vitro and in vivo, and promotion of cell apoptosis, demonstrating this pathway may become new therapeutic targets for RCCs. In this application, we will use anti-EPOR polyclonal antibody produced by ourselves, explore its binding ability with RCC cells and impact on EPO-EPOR pathway, observe the tumor growth curve in both vitro and vivo, and confirm its impaction on the proliferation, apoptosis and invasiveness of RCCs. We will also verify whether anti-EPOR antibody can be combined with current targeted drug to treat RCCs. This project will explore the therapeutic function of anti-EPOR antibody in RCC, confirm whether it can be used for treating RCCs, and provide new evidence for the treatment for RCCs.