MDA7/IL-24基因对CD133阳性肝癌肿瘤干细胞的作用与机制

项目名称： MDA7/IL-24基因对CD133阳性肝癌肿瘤干细胞的作用与机制

项目编号： No.81201673

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 王楠娅

作者单位： 吉林大学

项目金额： 23万元

中文摘要： 肝细胞癌是世界范围内公认的严重致死性恶性肿瘤之一，复发、转移、耐药等各因素严重限制了疗效的提高。肿瘤干细胞理论认为，肝癌的上述特点起源于肿瘤干细胞的存在。其中，CD133作为肝癌肿瘤干细胞重要标志物之一，被认为是治疗难治复发肝癌的重要靶点。抑癌基因MDA7/IL-24具有诱导凋亡、抑制血管新生、增加放化疗敏感性等多重抗癌效应。这些作用恰与CD133+肿瘤干细胞的生物学特征相拮抗，作用机制的信号传导通路位点也有交叉。本研究通过筛选CD133+肝癌干细胞，并建立CD133+肝细胞癌的动物模型。分析IL-24受体在CD133+肝癌干细胞及其肝癌组织中的表达情况，并将腺相关病毒介导MDA7/IL-24的基因用于CD133＋肝癌干细胞治疗，观察其抗癌作用及细胞传导通路各位点基因和蛋白的变化，为以CD133＋肝癌干细胞为靶点的基因治疗开辟新途径，也为复发难治肝癌治疗的转化性研究提供重要数据。

中文关键词： 肝细胞癌；肿瘤干细胞；CD133；MDA7/IL-24；

英文摘要： Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and is the third leading cause of cancer-related death worldwide. HCC therapy is challenged by the high recurrence rate, chemo-resistancy and metastatic potential. Since these challenges may be attributed to cancer stem cells (CSC), it is of interest to investigate if CSC targeting may be of value to CSC therapy. With identification of CD133 as an important cell marker of liver cancer stem cells, it is possible to evaluate the impact of therapeutic modality on the number and function of HCC CSC. Our previous studies and those by others have shown that MDA7/IL-24 not only selectively induces apoptosis in cancer cells, but also has immunomodulatory and antiangiogenic properties, as well as synergistic effect with chemotherapy and radiotherapy. Based on these observations, we seek to evaluate the impact of the MDA7/IL-24-based therapy on HCC CSC. We will first sort CD133+ cells from human CSC and establish their tumor-initiating activity in the nude mouse model. Then we will analysis the expression of MDA7 receptors IL-20R1/IL-20R2、IL-22R1/IL-20R2 in CD133+ CSC and their response to MDA7/IL-24. In addition to cell-instrinc response, we will also test the CSC-extrinsic impact of MDA7/IL-24. Our systemic analysis of impact of MAD7/IL-24 on HCC

英文关键词： HCC；Cancer stem cell；CD133；MDA7/IL-24；