元宝草以RXRα为靶点诱导肺癌细胞凋亡  

Hypericum sampsonii exerts its apoptotic activity on lung cancer cells through binding and inducing RXRα translocation

作　　者：韩春兰[1] 孙德福[2] 吴道军[3] 郭艳青[1] 王力[2] 亓建斌[4] 胡昌奇[4] 曾锦章[2] 

机构地区：[1]武警江苏总队医院,扬州225003 [2]中国科学院上海生命科学研究院,上海200233 [3]武警8714部队50分队,泉州362100 [4]复旦大学药学院,上海200032

出　　处：《武警医学》2007年第10期729-732,共4页Medical Journal of the Chinese People's Armed Police Force

基　　金：国家自然科学基金项目(30471939)

摘　　要：目的利用维甲酸受体(RXRα)为分子平台,从大量中草药提取物库中筛选可治疗肺癌的有效治疗药物,并深入研究其作用机制。方法实验中使用肺癌细胞系H460。利用配体-受体亲和实验以及报告基因系统筛选可作用于RXRα有效组分或化合物,利用免疫荧光检测RXR在细胞内的分布,用MTT法检测药物对细胞的生长抑制,用DAPI检测细胞的凋亡情况。结果发现元宝草中含有可结合RXRα并抑制RXRα转录活性的有效组分,这些组分为元宝草的醇提部位,在其馏分中主要位于氯仿萃取部位,这些有效部位可诱导肺癌细胞H460 RXRα出核,其作用依赖于细胞内RXRα的量,而且元宝草诱导RXRα出核在浓度上与细胞凋亡密切相关。结论中药元宝草提取物中含有可以直接结合RXRα的有效部位,其作用通过诱导RXRα出核和抑制RXRα转录活性而引起肺癌细胞H460的凋亡,这将为分离和开发这一药物提供重要的依据。Objective To screen apoptotic agents for treatment of lung cancer by traditional Chinese medicine based on RXRα- assay. Methods A lung cancer cell line,NIH- H460, was used in our experiment. In vitro RXRα binding assay was employed to screen compounds that target at RXRα. Growth suppression was detected by MTr colorimetric assay.Apoptotic morphology was observed by DAPI fluorescence staining. The location of RXR was detected by immunostaining. Results Ethanol extract of Hypericum sampsonii could directly bind to RXPα and the RXRα - targeting compound（s） was/were mainly contained in cholorform fraction. H. sampsoni inducied lung cancer cell NIH - H460 growth arrest and apoptosis was closely associated with RXRα nuclear export. On the other hand, H. sampsoni showed no effect on CV - 1 cells with undetectable RXRα When RXRα was introduced into CV- 1 cells, the growth inhibition induced by H. sampsoni was significantly recovered. When RXRα was introduced into lung cancer cell NIH - I-I460, growth inhibition and apoptosis induced by H. sampsonii were greatly enhanced.Conclusions H sampsonii contains ingredients that induce growth arrest and apoptosis of lung cancer cell NIH - I-I460 by targeting at RXRα.

关 键 词：元宝草 肺癌 RXRα 细胞凋亡 

分 类 号：R285.6[医药卫生—中药学]