miR-200c协同B16F10/mIL-21-GPI瘤苗降低黑色素瘤EMT并抑制其转移研究

项目名称： miR-200c协同B16F10/mIL-21-GPI瘤苗降低黑色素瘤EMT并抑制其转移研究

项目编号： No.81202372

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 赵枫姝

作者单位： 东南大学

项目金额： 23万元

中文摘要： 黑色素瘤高转移性是致死主要原因。我们前期研究显示IL-21-GPI黑色素瘤苗可增强免疫鼠细胞免疫,对荷瘤鼠有显著治疗效应，但仍不能抑制其转移。研究显示miR200c可抑制肿瘤细胞EMT。据此，本研究基于IL-21-GPI瘤苗免疫效应和miR200c表观遗传调节作用，探讨瘤苗和miR200c逆转黑色素瘤易转移的分子机制,为其根治提供新研究策略。首先以具有调节细胞增殖与凋亡、减低ZEB1表达的miR200c转染B16F10细胞，通过成球与克隆实验、细胞迁移及致瘤性等实验，评价miR200c对瘤细胞EMT的抑制作用；再以IL-21-GPI瘤苗免疫治疗B16F10/miR200c攻击所致的荷瘤鼠,检测肿瘤生长及瘤组织中miR200c、ZEB1及TGF-beta水平等，考核IL-21-GPI瘤苗与miR200c协同抑瘤和阻断瘤细胞EMT及转移效应，该研究对根治黑色素瘤有创新意义及潜在的临床应用价值。

中文关键词： 黑色素瘤；肿瘤疫苗；白细胞介素-21；微小RNA200c；上皮间质转化

英文摘要： Malignant melanoma is one of the deadliest forms of skin cancer and its incidence is expected to rise over the next two decades. At present, there are no effective therapies for advanced melanoma. Immunotherapeutic approaches for all kinds of cancers are currently emerging as promising strategies of anti-tumor therapy. Glycosylphosphatidylinositol (GPI) is a posttranslationally added lipid anchor and GPI-anchored membrane cytokines have been shown to play an important role in host immune response against tumor cells. Given that interleukin (IL)-21 is a T cell-derived cytokine that regulates an immune responses with the ability to regulate antitumor activity in mice, and generates considerable research interest in understanding their mode of action. We previous study suggested that administering whole tumor cell vaccine expressing IL-21 in the GPI-anchored form induced protective antimelanoma immunity in a B16F10 cell transplantable mouse model. However, an anti-melanoma efficacy was not completely satisfactory because the measurable tumors were detected in some mice , highlighting the need for studying combination and alternative strategies. Recent studies on tumour metastasis have provided proofs that microRNA?200c (miR200c) repress tumour 'epithelial to mesenchymal transition' (EMT) program that activates cell

英文关键词： melanoma；tumor vaccine；interleukin-21；miR200C；EMT