IL-11R介导的分子探针对前列腺癌及骨转移抗癌作用及机理研究

项目名称： IL-11R介导的分子探针对前列腺癌及骨转移抗癌作用及机理研究

项目编号： No.81202032

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： 孙晋

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 目前临床上尚缺乏对晚期前列腺癌（尤其是非雄激素依赖型前列腺癌）及骨转移有效的治疗手段，影响了前列腺癌患者的生活质量及生存期。课题组先期研究发现IL-11受体（IL-11R）能够作为前列腺癌及骨转移灶的潜在靶点，为此，提出假说：通过构建对IL-11R特异性靶向的分子探针，达到对前列腺癌及骨转移灶有效治疗目的。本项目拟进行放射性核素153Sm、抗癌中药藤黄酸（GA）分别标记对IL-11R具有高亲和力的九肽CGRRAGGSC，构建分子探针并进行稳定性、亲和力及生物活性检测；单独及联合应用标记探针对前列腺癌细胞及动物模型进行体内外干预，采用分子影像技术、病理学及分子生物学检测手段，从分子、细胞、组织及动物水平多层次探讨IL-11R介导的分子探针产生抗癌效应和可能发生的辐射增敏、增效减毒作用，阐明靶向治疗的分子机制，为前列腺癌及骨转移的有效治疗提供新的思路。

中文关键词： 白介素11受体；前列腺癌；骨转移；靶向治疗；分子探针

英文摘要： Currently there is no effective treatment on advanced prostate cancer (especially the androgen independent cancer) with bone metastasis. The life quality and survival duration of these patients is poor. Our early research showed interleukin 11 receptor would be a potential target for prostate cancer and bone metastasis. Based on this, we hypothesize a molecular probe for therapy use targeting IL-11 receptor could be an interesting treatment for prostate cancer and bone metastasis. In this project, we will use CGRRAGGSC, a nonpeptide with high affinity to IL-11 receptor, labeling with radionuclide samarium-153 or anticancer tranditional Chinese medicine gabogic acid (GA). These two molecular probes will be done respectively for stability, affinity and biological activity detection. Separated and combined application of these molecular probe will set up for in vivo and in vitro intervention study on cell lines and animal models, using multi-detection methods with molecular imaging, pathology and molecular biology technology. The purpose of this project is to find out the anti-cancer effects, possible radiation sensitization and synergistic effects, and potential mechanism of IL-11 receptor mediated molecular probes, that will open our minds for effective treatment on prostate cancer and bone metastasis.

英文关键词： Interleukin 11 receptor；prostate cancer；bone metastases；targeting therapy；molecular probes