蜂胶黄酮Pinobanksin-3-acetate对大肠癌细胞信号转导通路作用机制的研究

项目名称： 蜂胶黄酮Pinobanksin-3-acetate对大肠癌细胞信号转导通路作用机制的研究

项目编号： No.31260280

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 依米提·热合曼

作者单位： 新疆大学

项目金额： 46万元

中文摘要： 蜂胶黄酮Pinobanksin-3-acetate （PB3A）对大肠癌HCT116和SW480细胞具有明显的增殖抑制、细胞周期阻滞及诱导凋亡作用，但其抗肿瘤作用信号转导途径仍不甚清楚。通过人类全基因组表达谱芯片检测的54613个探针组中，SW480细胞 PB3A药物干预组与对照组相比表达上调的有551个基因，表达下调的有848个基因,其涉及细胞周期、凋亡、大肠癌发生等129个信号通路。我们拟选择Wnt/β-catenin及凋亡信号通路差异表达基因，采用实时荧光PCR和蛋白质免疫印迹法检测PB3A对基因转录和蛋白质表达的影响， RNA干扰技术沉默PB3A特异性下调表达基因，甲基化特异性PCR检测PB3A作用下差异表达基因的甲基化水平，旨在找出PB3A对大肠癌细胞作用的信号转导途径和基因靶点，阐明PB3A的抗肿瘤作用途径和开发其抗肿瘤效应，为新型肿瘤治疗策略的实施提供理论和实验依据。

中文关键词： 蜂胶黄酮；pinobanksin-3-acetate；基因芯片；差异表达特异性基因；信号通路

英文摘要： Propolis flavonoids Pinobanksin-3-acetate (PB3A) has a strong growth inhibitory effect, cell cycle arrest and induces cell apoptosis of human colorectal cancer (CRC) cell line HCT116 and SW480. However, the PB3A's anticancer signaling pathway remains to be further elucidated. The profiles of gene expression of CRC cell line SW480 control groups and PB3A intervention groups were analyzed by Human Genome Gene Chip Array U133, of the 54613 probe sets, compared with the control group cells, in result 551 genes were up-regulated by more than two folds and 848 genes were down-regulated by more than two folds in the PB3A intervention group cells. The differential expressed genes were correlated with cell cycle, apoptosis, and colorectal carcinogenesis etc 129 pathways of signal transduction. In our research, we have intend to choose Wnt/β-catenin and apoptosis related signaling pathways differential expressed genes, by using real time polymerase chain reaction(RT-PCR) and Western blotting assays to confirm the mRNA and protein expression level both in PB3A treated and untreated CRC cells. By using RNA interference (RNAi) to suppress drug untreated CRC cell's PB3A specific down-regulated genes. And using methylation-specific polymerase chain reaction (MSP) to determine PB3A specific differential expressed genes. Aims t

英文关键词： Propolis flavone；pinobanksin-3-acetate；Gene chip；Differentially expressed gene specificity；Signaling pathways