PNRC多肽通过干扰核受体途径抑制BT474细胞的增殖  

PNRC-derived peptidimer inhibits proliferation of BT-474 cells by interfering nuclear receptor signaling

作　　者：胡晨[1] 王越[2] 陈彬[2] 姜晓梅[2] 李渝萍[2] 娄桂予[2] 张艳[2] 何凤田[2] 周度金[2] 

机构地区：[1]第三军医大学学员旅8队,重庆400038 [2]第三军医大学生物化学与分子生物学教研室

出　　处：《现代肿瘤医学》2010年第6期1047-1050,共4页Journal of Modern Oncology

基　　金：国家自然科学基金项目(No30672055);重庆市自然科学基金项目(CSTC2006BB5352)

摘　　要：目的:运用核受体辅活化子PNRC的抗RasPTD融合多肽(PTD-PARP)研究其在乳腺癌细胞BT474中的分布、对核受体信号传导途径的影响及其抗肿瘤细胞增殖活性。方法:用多肽合成仪合成PTD-PARP、单独的PARP和PTD多肽以及FITC标记的PTD-PARP、PARP。HPLC分析和纯化后,荧光显微镜结合流式细胞仪检测PTD-PARP、PARP在BT474细胞中的分布。虫荧光素酶报告基因检测PTD-PARP对野生型PNRC辅活化ER反式激活功能的影响。MTS、软琼脂克隆形成实验检测PTD-PARP对BT474细胞的抗增殖活性。结果:PTD-PARP能进入BT474细胞,抑制野生型PNRC辅活化ER的反式激活功能并抑制BT474细胞的增殖。结论:PNRC抗RasP DT融合多肽可通过干扰核受体途径抑制乳腺癌细胞的增殖。Objective：To study the localization, the effect on nuclear receptor signaling and the anti -proliferation activity of a PNRC - derived peptidimer, PTD - PARP, in BT474 human breast cancer cells. Methods. Five polypeptides including PTD - PARP, PAR＇P alone, PTD alone and FITC - labelled PTD - PARP and PARP were synthesized by peptide synthesizer. All the polypeptides were anlysized and purified by high performance liquid chromatography （HPLC）. The localization of FITC - labelled PTD - PARP and PARP in BT474 cells was detected by fluorescence microscopy and FACS. The effect of PTD - PARP on the coactiviation of wild type PNRC to the trans - activity of ER was evaluated by luciferase reporter assay. The anti - proliferation activity of PTD - PNRC in BT474 cells was detec- ted by MTS and colony formation in soft agar. Results： PTD - PARP can localized in BT474 ceils, and inhibit the co- activiation of wild type PNRC to the transactivity of ER. The peptide can inhibit the proliferation of BT474 in a dos- age - dependent manner. Conclusion： An anti - ras PTD fused PNRC - derived peptidimer can inhibit the proliferation of BT474 calls by interferring nuclear receptor signaling.

关 键 词：PNRC 多肽 PTD 核受体 信号传导 

分 类 号：R730.54[医药卫生—肿瘤] R737.9[医药卫生—临床医学]