谷糠结合态多酚通过miRNA-149逆转结肠癌多药耐药的活性成分及分子机制

谷子（Setaria italica）属一年生禾本科植物，谷糠是谷子加工成小米的过程中脱下的副产品，有研究表明谷糠源多酚具显著的抗肿瘤功效。肿瘤多药耐药是肿瘤治疗的最大难题之一，而miRNAs在调控肿瘤耐药网络中扮演了关键角色。本课题组研究发现，谷糠结合态多酚BPIS能够通过上调miRNA-149逆转结肠癌的多药耐药性。因此，本项目拟探讨BPIS中通过miR-149逆转结肠癌耐药的活性成分及分子机制。研究内容包括：采用多种色谱技术分析BPIS成分并鉴定单体结构；用结肠癌多药耐药细胞和裸鼠模型确定BPIS中逆转结肠癌耐药的活性成分，BPIS-R；从转录因子及表观遗传学两个方面探讨BPIS-R对miR-149表达水平的调控方式；筛查miR-149调控结肠癌多药耐药的靶基因；构建敲除或过表达该靶基因的多药耐药细胞和裸鼠模型，确定其介导BPIS-R逆转结肠癌多药耐药的关键角色。

Foxtail millet (Setaria italica) is an annual plant, and millet bran is naturally rich by-product produced during the milling of millet. Previous studies had shown that polyphenols in millet bran exhibited significant anti-tumor effects. Multidrug resistance（MDR）is a biggest problem of tumor therapy, and miRNAs play key roles in the MDR regulation. Currently, we uncover that bound polyphenol of inner shell（BPIS）from millet bran can reverse the multidrug resistance of colon cancer cells (CRC) by up-regulating the miRNA-149 expression. Therefore, this project aims to explore the active constituents that display the MDR reversal of CRC in BPIS by miR-149 and its molecular mechanism. The contents are as follows: analyzing the chemical components of BPIS and identifying the compound structures by various chromatographic techniques; Confirming the active ingredient in BPIS that possesses the MDR reversal of CRC both in vitro and in vivo, named BPIS-R; Investigating the main way that BPIS-R regulates the expression level of miR-149; Screening the target genes of miR-149 to regulate the MDR of colon cancer; Constructing the stable MDR cell and nude mouse models by knock-outing or over-expressing target gene to determine the key role of its in mediating the MDR reversal of CRC by BPIS-R-induced.