TV-miR-200b/c靶向抑制HER2/HER3克服乳腺癌对赫赛汀耐药

项目名称： TV-miR-200b/c靶向抑制HER2/HER3克服乳腺癌对赫赛汀耐药

项目编号： No.81472469

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐海林

作者单位： 中山大学

项目金额： 78万元

中文摘要： 申请者前期证实miR-200b在胃癌、胶质瘤及乳腺癌组织和细胞中表达下调，过表达miR-200b可抑制肿瘤细胞生长侵袭（Tang,et al. Cancer Lett; J Transl Med; Med Oncol），miR-200b/c可靶向DNA甲基化转移酶调控全基因组甲基化水平（Tang, et al. Clin Cancer Res），联合miR-200b和miR-200c能选择性抑制HER2阳性乳腺癌生长，增加赫赛汀耐药的乳腺癌细胞的敏感性。自主发明的TV-miR-200b/c能诱导HER2阳性乳腺癌细胞凋亡并抑制HER2、HER3表达。本项目通过DNA甲基化转移酶等探讨TV-miR-200b/c调控HER2/HER3诱导乳腺癌的分子机制及TV-miR-200b/c克服赫赛汀耐药的作用，为TV-miR-200b/c作为一种新的HER2/HER3的靶向药物提供实验依据。

中文关键词： C21_乳腺肿瘤；微小RNA

英文摘要： Our previous data demenstrated that miR-200b was down-regulated in gastric cancer, glioma and breast cancer tiussues and cells. Overexpression of miR-200b inhibited tumor cells proliferation and invasion (Tang, et al. Cancer Lett; J Transl Med; Med Oncol). MiR-200b/c reduced the levels of global DNA methylation (GDM) by targeting DNA methyltransferases（Tang, et al. Clin Cancer Res）. We further found that miR-200b combining with miR-200c inhibited HER2+ breast cancer cells selectively and re-sensitized herceptin-resistant cells to herceptin. Self-created TV-miR-200b/c could induce apoptosis of HER2+ breast cancer cells and inhibit the protein expression of HER2 and HER3. In this project, we will confirm the effects of TV-miR-200b/c on regulating HER2/HER3 expression and carcinogenesis of HER2+ breast cancer. In addition, the role that TV-miR-200b/c possesses therapeutic potential to overcome herceptin resistance will be elucidated. In conclusion, this project will provide experimental evidences for developing TV-miR-200b/c as a novel therapeutic strategie in HER2+ breast cancer treatment.

英文关键词： breast cancer;miRNA