miR-663在长梗秦艽酮诱导非小细胞肺癌细胞凋亡过程中的作用及其机制研究

项目名称： miR-663在长梗秦艽酮诱导非小细胞肺癌细胞凋亡过程中的作用及其机制研究

项目编号： No.81201833

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2

项目作者： 张毅

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： MicroRNA(miRNA)在肺癌的发生发展过程中发挥重要作用,可以成为药物治疗肺癌的作用靶标。萜类化合物具有良好的抗肿瘤作用，长梗秦艽酮是从长梗秦艽中分离得到的一个萜类化合物，国内外研究发现其有明显抗肿瘤作用。在前期研究中我们发现长梗秦艽酮对肺癌A549细胞有较强的抑制作用，可抑制细胞的增殖、诱导细胞凋亡；同时发现药物作用前后伴随miR-663表达增加，相关文献已证实miR-663作为抑癌基因在多种肿瘤中发挥作用，其可能成为肺癌药物治疗的靶标。本研究拟在前期研究的基础上，通过实时定量PCR、转染、免疫印迹、双荧光素酶报告等研究方法，进一步探明长梗秦艽酮诱导非小细胞肺癌细胞凋亡的分子机制,并探讨miR-663在其中所起的调控作用。揭示长梗秦艽酮抑制非小细胞肺癌增殖与诱导细胞凋亡的作用靶标，为临床长梗秦艽酮辅助治疗非小细胞肺癌提供理论依据，为研制和开发抗肿瘤创新药物奠定基础。

中文关键词： 微小RNA；非小细胞肺癌；长梗秦艽酮；凋亡；

英文摘要： MicroRNA (miRNA) play an important role in the development and progression of human lung cancer. While altered expression of miRNAs would be the important application for discovering effective targets and mechanisms in treatment of cancer with anticancer agents. Waltonitone was isolated from Gentiana waltonii Burkill, which has been successfully used for centuries in Chinese folk medicine. Recent studies have shown that waltonitone could inhibited growth of cultured cells in few human carcinoma cell lines. In our previous study, we found that waltonitone could inhibit the proliferation of A549 cell and induce cell apoptosis. We also found that waltonitone upregulated the expression of miR-663. MiR-663, which downregulated in many cancer, may be a target for drug treatment. To further understand the mechanisms of action of waltonitone against the growth of human lung cancer A549 cells, we investigated the role of miR-663 in it using real-time PCR, transfection, western blotting，luciferase assays and other methods. It will supply experimental basis for the further investigation of anti-cancer mechanism of waltonitone, and will provide the theoretical basis for clinical treatment of non-small cell lung cancer.

英文关键词： microRNA；non-small cell lung cancer；waltonitone；apoptosis；