miR-376b 介导的细胞自噬在羟基酪醇逆转肝癌耐药中的作用及其机制研究

项目名称： miR-376b 介导的细胞自噬在羟基酪醇逆转肝癌耐药中的作用及其机制研究

项目编号： No.81502069

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 赵宝磊

作者单位： 滨州医学院

项目金额： 18万元

中文摘要： 化疗耐药是肝癌治疗失败的主要原因之一，我们前期研究证实，羟基酪醇可有效抑制肝癌细胞的增殖及裸鼠原位肝癌的生长，进一步研究证实羟基酪醇可逆转肝癌耐药细胞的耐药性，但其作用机制尚未阐明。近年来，microRNAs 通过对基因表达的调控参与逆转化疗耐药的作用日益受到重视，本课题尝试从这一崭新角度研究羟基酪醇逆转肝癌耐药作用及其可能机制。本项目拟以肝癌阿霉素耐药细胞株为研究对象，采用 miRNA 芯片和生物信息学等手段筛选出羟基酪醇逆转肝癌耐药相关的关键性miRNA-miR-376b及其作用靶点Beclin1，通过基因克隆和RNA 干扰等技术干扰miR-376b表达，在细胞和动物模型中探讨miR-376b 在羟基酪醇逆转肝癌耐药中的作用及其调控机制，为针对肝癌耐药的治疗提供新的靶点，并开辟羟基酪醇抗肿瘤作用机制研究的新思路，为其进一步开发利用提供更充分的科学依据。

中文关键词： 肝癌；羟基酪醇；microRNA；；化疗耐药

英文摘要： The emergence of chemoresistance within tumour cells is one of the main reasons for treatment failure of HCC. Our previous studies have demonstrated that hydroxytyrosol could effectively suppress the growth of hepatocellular carcinoma in vitro and in orthotopic hepatocellular carcinoma in nude mice. Further studies confirmed that hydroxytyrosol could overcome the multidrug resistance in multidrug-resistant human hepatocellular carcinoma cell lines, however, its exact mechanism is not clear. Recently, more and more studies have focused on the role of microRNAs in the regulation of MDR. As a result, We will attempt to study the effect of hydroxytyrosol on overcoming MDR in hepatocellular carcinoma from this point of view. In this study, we used miRNA chips to screen differentially expressed miRNA in HCC cell lines resistant to doxorubicin when treated with hydroxytyrosol，and then found the crucial miRNA-miR-376b and its target gene- Beclin1 using bioinformatics method. We will then explore the effect of miR-376b on overcoming MDR of HCC and its possible mechanisms. Our study is designed to test the interactions and mechanisms of miR-376b in the process of overcoming MDR in hepatocellular carcinoma by hydroxytyrosol, provide a new therapeutic target for HCC and adequate evidence for the anti-cancer effects of hydroxytyrosol.

英文关键词： Hepatocellular carcinoma;Hydroxytyrosol;microRNA ;Chemoresistance