紫草有效成分抗癌应用的探索及其分子机制的分析-exploration of anticancer application of effective components of arnebia euchroma and analysis of its molecular mechanism.docxVIP

PAGE 10 PAGE 10 英 文 摘 要 which is a ligand of RXRα, when study its effects on homologous transactiva- tion. While co-transcripted RXRα expression plasmid, TR3 or RAR expres- sion plasmid and CAT reporter vector containing TREpal in study of its effects on heterogenous transactivation. And the the amount of chloramphenicol ace- tyltransferase with 3H tag can be measured by Scintillation Counter in the unit of cpm. Results：We found 1 Zicao can inhibit lung cancer cell line H460, while co-treat with 9-cis-RA , its inhibition effect was alleviated; 2 Ligand binding assay indicated crude zicao extract can bind with RXR, and separates half of [3H] 9-cis-RA binding with RXR when Zicao is at the concertration of 1μg/ml ; 3 RXR protein degrades in H460 when treated with Zicao, indicating Zicao impares RXR stability; 4 More data on various active ingredients of Zicao demonstrate that many shikonin derivates, such as sk02, can bind with RXR and down regulate its both homologous and heterogenous transactivation; 5 SK02 repress proliferation of CV-1 cell line express high-level RXR more strongly than control; 7 SK02 makes the RXR Ligand Binding Domain refold after binding with it; 8 SK02 promotes the degradation of RXR. Conclusion：Zicao suppresses tumor gowth by modulating RXR trans- activation and its protein stability. Keywords：Zicao; shikonin; RXR; lung cancer 研 研 究 论 文 紫草有效成分抗癌应用的探索及其分子机制的研究 前 言 1.紫草简介 紫草是紫草科拟紫草属植物新疆紫草 Arnebia euchroma (Royle) Johnst. 或内蒙紫草 Arnebia guttata Bunge 的干燥根。性甘、咸、寒。具有 凉血，活血，解毒透疹的功效，用于血热毒盛斑疹紫黑，麻疹不透，疮疡， 湿疹，水火烫伤[1]。 早在几个世纪之前，紫草就分别被东方和西方用来作为药物。在中国， 紫草最初是作为红色染料给丝织品染色。华佗首先把紫草用于医药制成抗 菌和抗感染的药膏[2]。《本草纲目》记载；“紫草，其功长于凉血，利大、 小肠，故豆疹欲出未出，血热毒盛，大便闭涩者宜用之”。 在欧洲，对紫草的记载最早见于古希腊的医学家和哲学家希波克拉底 （公元前 4，5 世纪）的著作。记录了紫草用于治疗皮肤溃疡[3]。植物学 家和学者泰奥弗拉斯托斯（公元前 3，4 世纪）也记录了紫草在染料和医 药方面的应用[4]。亚历山大大帝就曾经用紫草来治疗受伤的士兵。 1.1 紫草的活性成分 紫草素首先被日本化学家 Majima 和 Kuroda 以酯的形式分离出来。 Brockmann 更正了他们提出的紫草素的结构，提出了紫草素以存在两种旋 光异构体：紫草素和紫草宁[5]（图 1）。 Papageorgiou 将紫草粗提物分离成蜡，荧光物质，天然多聚体，以及 色素四个组分。分别将各个组分给诱导溃疡的实验动物服用。P