椿皮中苦木内酯类成分抑制HER2的作用机制和构效关系研究

项目名称： 椿皮中苦木内酯类成分抑制HER2的作用机制和构效关系研究

项目编号： No.81202428

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： 王文婧

作者单位： 暨南大学

项目金额： 24万元

中文摘要： 乳腺癌是女性常见的恶性肿瘤之一，其发病率高居女性肿瘤疾病首位，并且呈明显的上升趋势。HER2作为乳腺癌恶性程度、术后复发及预后风险的重要指标，是目前国内外研究治疗乳腺癌药物的主要靶标。我们在前期工作中，从臭椿中分离鉴定了多种骨架类型的苦木苦味素类化合物，活性结果显示，该类成分具有显著的抗乳腺癌活性，且毒性较小，初步的作用机制研究提示该类成分抗乳腺癌与HER2酪氨酸激酶有关。本项目拟在前期工作基础上，进一步对臭椿中的苦木苦味素类化合物进行系统分离，并评价和研究该类成分抗乳腺癌的生物活性、作用机制及构效关系，为研究和开发选择性高、毒副作用小的抗乳腺癌药物提供科学依据。

中文关键词： 臭椿；苦木内酯；HER2；作用机制；构效关系

英文摘要： Breast cancer is one of the common malignant tumors for female patients. The incidence of breast cancer is the first amomg the female malignant tumors and remains a significantly increasing rate. HER2, an important marker of malignancy, postoperative recurrence and prognosis for breast cancer cases, is considered as the potential drug target. In our searching for bioactive constituents with unique structure from traditional Chinese medicines, 14 quassinoids with different skeletons were isolated from the EtOH extract of the barks of Ailanthus altissima. And these quassinoids showed potent selective cytotoxic activities against breast cancer cells. Furthermore, mechanistic study indicated that the cytotoxicity of quassinoids was associated with the inhibition of HER2 tyrosine kinase enzyme. On the basis of previous work, the present study will focus on the mechanism and structure-activity relationship of the quassinoids for their anti-breast cancer activities. Our study will provide scientific basis to development of new anti-cancer drugs with higher efficacy and lower toxicity for the treatment of breast cancer.

英文关键词： Ailanthus altissima；quassinoids；HER2；mechanism；structure-activity relationship