项目名称: 木香挥发油抗肝癌的药效评价及作用机制研究
项目编号: No.81503307
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: 彭章晓
作者单位: 中国人民解放军第二军医大学
项目金额: 18万元
中文摘要: 木香烃内酯(Cos)和去氢木香内酯(Dehy)为主的倍半萜类化合物是木香挥发油(VOSL)的主要活性成分,具有抗炎、抗癌、抗病毒、抗菌、抗氧化、抗溃疡,等广泛的药理活性。我们前期研究表明VOSL在体内具有高效、低毒的抗癌活性,其抗癌效果优于单个化合物Cos或Dehy的效果,体现了“多成分、多靶点、协同治疗”的特点。研究表明Cos 和Dehy具有很好的抗乙肝病毒活性,而我国85%-90%的肝癌都与乙肝有关,因此VOSL的抗病毒和抗癌的双重活性使其具有很好的临床应用前景。本研究中,我们将选取五种人源肝癌细胞系,利用细胞增殖、周期、凋亡、Transwell等实验,评价VOSL、Cos、Dehy的体外抗肝癌效果,筛选对测试物敏感的肝癌细胞系进行动物模型实验,在体内进一步评价其抗肝癌效果。我们还将采用代谢组学、蛋白组学等多组学策略结合分子生物学技术,探索VOSL“多成分,多靶点”的抗癌作用机制。
中文关键词: 木香挥发油;肝癌治疗;作用机制;代谢组学;蛋白组学
英文摘要: Volatile oil from saussurea lappa Dence (VOSL), including two main sesquiterpene lactones, costunolide (Cos) and Dehydrocostus lactone (Dehy), possess various biological activities, including anti-inflammatory, anticancer, antiviral, antimicrobial, antioxidant, antiulcer, etcetera. Our previous researches have demonstrated that VOSL performed a better anti-cancer activity with lower toxicity in vivo than Cos or Dehy, and had “multiple-components, multiple-targets, and synergistic” anti-cancer effects. Moreover, Cos and Dehy had been reported that they had good anti-hepatitis B virus. Statistically,about eighty-five to ninety percent of liver cancer accompanied with hepatitis B in our country. Therefore, VOSL should be an attractive anti-liver cancer agent due to its dual activities of anti-cancer and anti-hepatitis B virus. In this study, we will evaluate the anti-liver cancer effects of VOSL, Cos and Dehy on five human liver cancer cell lines with the experiments of cell proliferation assay, cell cycle assay, cell apoptosis assay, transwell assay, and so on. Then, the most sensitive cell line for the tested compounds will be used to make the liver cancer xenograft mouse model, and the anti-liver cancer activities of the tested compounds will be further evaluated in vivo. Moreover, we will adopt “multi-omics” technology, including metabonomics and proteomics, and molecular biotechnology to explore “multiple-components, multiple-targets, and synergistic” anti-cancer mechanism of VOSL.
英文关键词: Volatile oil from saussurea lappa Dence;Liver cancer treatment;Molecular mechanism;Metabonomics;Proteomics