Notch信号通路在姜黄素介导光动力治疗宫颈癌的作用研究

项目名称： Notch信号通路在姜黄素介导光动力治疗宫颈癌的作用研究

项目编号： No.81202966

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 贺桂芳

作者单位： 中日友好医院

项目金额： 23万元

中文摘要： 宫颈癌是当前妇女第二大恶性肿瘤，发病率高且趋于年轻化。Notch信号通路与其发生发展密切相关。手术创伤、放化疗对患者卵巢和阴道功能造成严重毁损。而光动力治疗（PDT）是无创、有效的肿瘤新疗法之一，因能保留器官和生育功能而极具诱人前景。我们前期研究表明，光动力治疗宫颈癌是有效手段。姜黄素作为一种高效、低毒的抗癌新药和光敏剂，与PDT具有协同和互补作用，已应用于鼻咽癌、基底细胞癌等其它恶性肿瘤治疗。本课题拟以姜黄素为光敏剂，通过从细胞、分子水平观察姜黄素介导PDT对宫颈癌Me180细胞的最佳作用参数、分析治疗前后Notch及下游NF-κB、COX-2、VEGF-A、-C、VEGFR-3各环节发生的作用，在此基础上进一步从整体水平观察PDT对宫颈癌动物模型的影响，同时通过阻断剂阻断Notch受体，以明确Notch在PDT治疗宫颈癌中的可能作用靶点，为临床光动力治疗宫颈癌提供新思路和实验依据。

中文关键词： 姜黄素；光动力治疗；宫颈癌；Notch信号通路；

英文摘要： Cervical cancer is the 2nd most frequently occurred tumor in female reproductive system in the world. And its incidence rate is high and rapidly increasing among young women. Notch signaling pathway closely correlates with carcinogenesis and development of cervical cancer, is a potential control-target to improve the effectiveness of PDT. Traditional treatment, like surgery and radio/chemo therapy, could cause serious damage to ovarian and vaginal functions. While photodynamic therapy (PDT), as its high possibilities to retain patients' organ and reproductive function, is a new and effective noninvasive therapy to cancers with bright prospect. Our preliminary studies demonstrated that, PDT is an effective measure for cervical cancer treatment. Curcumin, as a high efficiency and low toxicity anti-cancer drug and photosensitiser, has co-activation and complemention effects with PDT. It has been proven in treatment of some malignant tumor, such as nasopharyngeal carcinoma and basal cell carcinoma. Our study is aiming to find, on both cellular and molecular levels, the optimal interaction parameters of curcumin mediated PDT on cervical cancer cell, Me180; analyze the role of Notch and downstream genes, such as NF-KB, COX-2, VEGF-A, VEGF-C, and VEGFR-3, before and after PDT; based on which, to further observe the

英文关键词： curcumin；photodynamic therapy；cervical cancer；Notch signaling pathway；