以FGF8为靶点的前列腺癌分子显像与治疗研究

项目名称： 以FGF8为靶点的前列腺癌分子显像与治疗研究

项目编号： No.81460270

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李娟

作者单位： 宁夏医科大学

项目金额： 47万元

中文摘要： 已发现FGF8在前列腺癌中高表达，通过MEK1/2、PI3K等途径诱导肿瘤血管生成，发挥促癌作用。通过噬菌体肽展示文库筛选的多肽HSQAAVP（HAP）与FGF8b具有高亲和力，有望成为肿瘤治疗的新靶点。结合核素示踪技术，我们假设99mTc-HAP能够在动物体内观察到FGF8b的分布和表达量，可用于前列腺癌早期诊断；131I-HAP能够靶向治疗前列腺癌，辐射吸收剂量安全。前期工作中，我们已验证FGF8b在77.5%的前列腺癌中呈高表达，Confocal示HAP与LNCaP细胞呈强绿色荧光信号， 99mTc-HAP在荷瘤裸鼠体内显像效果好。结合前期基础，本项目拟选择不同肿瘤细胞系，通过Confocal、Western blot、FCM技术，拟阐明HAP抑癌机制；合成99mTc/131I-HAP分子探针，评价SPECT/CT分子显像和靶向治疗效果，为前列腺癌早期诊断和靶向治疗提供新的方法。

中文关键词： 放射性核素显像；分子探针；FGF8；靶向治疗；前列腺癌

英文摘要： It is known that Fibroblast growth factor-8 (FGF8) has proven to be highly expressed in prostate cancer. FGF8 plays an important role in tumorogenesis by inducing angiogenesis under MEK1/2, PI3K pathways. It promotes not only tumorigenesis but also metastasis. Peptide HSQAAVP was isolated as a specific FGF8b-binding phage clones by screening a phage peptide display library. And due to its highly affinity with FGF8b, it is expected to be a new target for prostate cancer treatment. Nuclide tracing technique shows dynamic changes of target molecules in vivo and noninvasively, and helps diagnosis and therapy of diseases by molecular levels. Combined with nuclide tracing technique, we hypothesize the following three points of view. Firstly, 99mTc-HSQAAVP can be radiolabeled and display the expression and distribution of FGF8b in vivo. Secondly, 131I-HSQAAVP can be radiolabeled and serve in targeting therapy of prostate cancer. Thirdly, HSQAAVP suppresses the occurrence and progression of prostate cancer by inhibiting tumor cell proliferation and occurance of EMT. In previous experiments, we found the expression of FGF8b increased in 77.5% of prostate cancer specimens; HSQAAVP and LNCaP cells showed strong green fluorescence signal in Confocal images. SPECT imaging with 99mTc-HSQAAVP in nude mice bearing prostate carcinomas showed clearly uptake in tumors. Based on the former results, in this project we plan to apply molecular biologic technologies, such as Confocal imaging, Western blot, FCM, to clarify the molecular mechanism of HSQAAVP inhibiting tumor development; synthesize 99mTc/131I-HSQAAVP molecular probes to evaluate their functional effects as new biomarkers in early diagnosis and targeting therapy for prostate cancer. We are looking forward that the new molecular probes can offer a new approach to diagnosis and therapy of prostate cancer.

英文关键词： Radionuclide Imagine;Molecular Probe;FGF8;Targeting Therapy;Prostate Cancer