土木香根中5种倍半萜化合物抗肝癌活性的研究  

Anti-human hepatoma activity of five sesquiterpenoids from Inula helenium

作　　者：陈进军[1] 赵路 董玫[3] 王思明[4] 秦琪瑜[1] 陈虎[1] 史清文[3] 

机构地区：[1]河北医科大学第一医院肝胆外科 [2]北京军区66010部队卫生队 [3]河北医科大学基础医学院法医学系河北省法医学重点实验室 [4]河北医科大学药学院

出　　处：《癌变．畸变．突变》2010年第6期440-443,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(8107255);河北省自然科学基金(08B032;C2010000489);河北省留学回国人员科技活动项目(2006-02)

摘　　要：目的:检测菊科植物土木香中分离出的5种倍半萜类化合物对肝肿瘤活性的影响,探讨这5种倍半萜类化合物结构与活性之间的关系以及可能的作用机制。方法:利用噻唑蓝(MTT)比色法检测5种倍半萜类化合物对人肝肿瘤细胞增殖活性的影响;以移植性小鼠肝肿瘤H22为模型,检测异土木香内酯对昆明小鼠在体肿瘤生长以及机体免疫能力的影响;以体外培养的人胚肺成纤维细胞为模型,评价异土木香内酯对正常细胞的毒性。结果:异土木香内酯对人肝肿瘤细胞(HLE)的增殖显示较强的抑制活性;其余4种化合物对HLE的增殖不显示抑制活性;异土木香内酯对小鼠移植性肝肿瘤H22体内生长具有较强的抑制活性,但对荷瘤小鼠胸腺指数和脾指数的影响与对照组相比差异均无统计学意义(P>0.05);异土木香内酯对体外培养的人胚肺成纤维细胞显示较弱的毒性。结论:异土木香内酯具有较强的抗肝癌活性;其它4种倍半萜类化合物抑制活性的丧失可能是由于化合物中五元内酯环的环外双键饱和所致,或A、B环的C5-C10键断开生成十元大环所致;增加机体免疫能力可能是异土木香内酯抗肝肿瘤的作用机制之一。OBJECTIVE： To assess the anti-human hepatoma effects of five sesquiterpene lactones from the roots of Inula helenium,and to explore the relationship between structure and activity and the possible mechanism of antitumor action.METHODS： Using MTT assay to evaluate the antitumor activities of five sesquiterpene lactones on the human hepatoma cell line HLE,and to explore the cytotoxicity on human embryonic lung cells.The rate of cell proliferation was determined by grafted tumor assay in vivo.RESULTS： Isoalantolactone exhibited significant anti-proliferative activities to hepatoma cell,while other compounds demonstrated weak anti-proliferative activities.Isoalantolactone significantly inhibited tumor growth of H22 tumor-bearing mice.Isoalantolactone showed no toxicity to human embryonic lung cell line in vitro.CONCLUSION： These results clearly demonstrated that the anti-tumor activities had close relationship with the structures,β-unsaturated five-membered lactone ring was necessary for the activities.When β-unsaturated five-membered lactone become saturated or the bond between C-5 and C-10 of ring-A and ring-B broken to form a 10-membered macroring,anti-proliferative activity was either diminished or lost.

关 键 词：土木香 倍半萜类化合物 人肝肿瘤细胞 增殖抑制活性 构-效关系 

分 类 号：R730.1[医药卫生—肿瘤]