Physcion（大黄素类似物）抑制乳腺癌细胞转移分子机制研究

项目名称： Physcion（大黄素类似物）抑制乳腺癌细胞转移分子机制研究

项目编号： No.81202550

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 张陈

作者单位： 同济大学

项目金额： 23万元

中文摘要： 肿瘤转移是肿瘤致死的主要原因,大量研究数据表明从天然产物中获取低毒的抗肿瘤分子是非常有效的手段。近期我们以HT1080细胞系为模型，率先证明了三羟基蒽醌类天然化合物physcion通过抑制金属基质蛋白酶（MMP）表达起到了显著的抗肿瘤转移作用，并且在乳腺癌细胞中同样获得了有效验证。本研究拟通过动物造模肿瘤血行转移模型，进一步证实physcion对乳腺癌细胞的抗转移作用，通过基因表达谱芯片和下游信号通路分子的功能验证，进一步揭示physcion抑制肿瘤细胞转移的内在分子机制， 并从细胞和动物水平，对physcion的潜在治疗效果进行综合评估，因此本项目的研究将不仅为揭示physcion的抗肿瘤机制提供进一步的数据，也为将其发展成抗肿瘤药物建立一个评估体系。

中文关键词： 大黄素甲醚；抗肿瘤转移；分子机制；ADRBK1；乳腺癌

英文摘要： Cancer is a class of diseases with uncontrolled growth, invasion and metastasis characters, cancer metastasis is the major cause of cancer mortality, and a great deal of attention has been led to discover potential pharmaceutical compounds as anti-metastasis candidates. In the Previous study, natural compound physcion, an analogue of emodin, isolated from nature product. It has been inventively proved it can significantly inhibit the cancer cell migration, invasion, and metastasis in HT1080 cells by down regulation MMP-2 and MMP-9 expressions. Besides, physcion also can inhibit MCF-7 cells, which have no MMP-2 and MMP-9 expressions. This project intends to do further research on the previous results, confirm the physcion inhibit the metastasis of breast cancer cells by animal metastasis model, and investigate the correlative molecular mechanisms of this inhibitory effect. These contents, establish the theoretical foundation for the future analysis the anti-tumor metastasis applications of physcion, further more establish an evaluation system for developing anticancer metastasis drugs.

英文关键词： Physcion；Anti-tumor metastasis；Molecular mechanisms；ADRBK1；Breast cancer