姜黄素（CUR）经Ⅱ期临床研究表明是一种安全性较好而活性不高的抗癌药物。为此，我们对CUR进行一系列结构修饰（专利申请号：CN201310067406.7），经细胞和动物实验发现其中一种新构型CUR衍生物CURD-17具有高活性的抗肝癌作用，且对正常肝细胞L-02几乎无抑制，但CURD-17抗肝癌作用的分子机制尚不明确。本项目拟以CUR为对照，将对CURD-17进行l两个方面的研究：1.考察CURD-17对BEL-7402和HepG2肝癌细胞的增殖抑制、周期及凋亡的影响,并采用RT-PCR及Western blot方法确证其作用靶点基因及蛋白；2.构建裸鼠肝癌模型，考察CURD-17抗肝癌作用并确证其作用靶点基因及蛋白。以此阐明CURD-17抗肝癌作用及分子机制，为CURD-17抗肝癌应用提供科学的理论依据和实验指导

A phase II clinical trial shows that curcumin (CUR) is a highly safe antitumor agent, but has a low antitumor activity. Therefore, a series of structural modification of CUR as a lead compound was carried out by us in previous study (Patent application number: CN201310067406.7).Among the resulted compounds, a novel structural derivative of CUR (CURD-17)showed high inhibitory activity against hepatocellular carcinoma cells and its subcutaneously transplanted tumor model, furthermore，had few inhibitory effect on human normal liver L-02 cells. But, the molecular mechanism of action of CURD-17 against hepatocellular carcinoma still remains unknown. Therefore, compared with CUR, three main aspects of CURD-17 will be studied in the present reseach.1.Gene chip technology will be used to detect differentially expressed genes to confirm its key adjustable target.2.Evaluation of the effect of CURD-17 on proliferation inhibition, cycle distribution and apoptosis of BEL-7402 and HepG2 hepatocellular carcinoma cells, and validation of its key target genes and proteins by RT-PCR and Western blot.3.Establishment of the orthotopic transplantation model of hepatocellular carcinoma in nude mice, experimental study on the antitumor effect of CURD-17 and validation of its key target genes and proteins. The objective of this study is to clarify antitumor activity and molecular mechanism of CURD-17 against hepatocellular carcinoma. This study is to provide scientific and theoretical evidence and experimental guidance for CURD-17 used in the treatment of hepatocellular carcinoma.