| 靶向肺癌干细胞的海绵抗肿瘤活性化合物的发现 |
| 投稿时间：2017-03-28 修订日期：2017-05-10 点此下载全文 |
| 引用本文：刘曼,刘丽云,孙凡,林厚文.靶向肺癌干细胞的海绵抗肿瘤活性化合物的发现[J].药学实践杂志,2017,35(4):304~307 |
| 摘要点击次数: 1644 |
| 全文下载次数: 1511 |
|
| 基金项目:国家自然科学基金-联合基金项（U1605221）；国家自然科学青年基金项目（81502936）；上海交通大学医学院转化医学协同创新中心（TM201509） |
|
| 中文摘要:目的 追踪并分离海绵Aaptos aaptos中靶向抑制肺癌干细胞的活性化合物。方法 首先构建肺癌干细胞A549-Nanog-GFP的药物筛选模型，用Western blot和免疫荧光验证构建的肺癌干细胞模型中干性基因的表达。利用肺癌干细胞模型对海绵Aaptos aaptos二氯甲烷萃取物的8个组分进行活性初筛，采用多种色谱分离手段对活性部位进行分离，用CCK8法对分离得到的化合物进行体外抗肺癌干细胞活性筛选。结果 成功构建了高表达CD44和ALDH1A1蛋白的肺癌干细胞模型；初筛发现组分D6具有显著的肺癌干细胞抑制活性（P<0.01）；从组分D6中分离得到4个aaptamine类生物碱，化合物AP-1具有显著的抗肺癌干细胞活性（P<0.01），其IC50值为（3.84±0.12）μmol/L。结论 海绵Aaptos aaptos提取物中分离得到的aaptamine类生物碱AP-1具有良好的抗肺癌干细胞活性。 |
| 中文关键词:aaptamine类生物碱 肺癌干细胞 增殖 AP-1 |
| |
| The discovery of antitumor compounds from marine sponge targeting lung cancer stem cells |
|
|
| Abstract:Objective To screen the active compounds targeting lung cancer stem cells (LCSCs) from the sponge Aaptos aaptos. Methods The A549-Nanog-GFP model of LCSCs was constructed. Western blot and immunofluorescence were used to examine the expression of pluripotency markers in screening model. The established LCSCs model was used to screen 8 fractions of Aaptos aaptos dichloromethane extract. The active fraction was separated by various chromatographic methods. CCK8 assay was used to screen the compounds for anti-LCSCs activity in vitro. Results LCSCs model with high expression of CD44 and ALDH1A1 protein was successfully constructed. The fraction D6 showed significant inhibitory activity in LCSCs(P<0.01). Four aaptamine alkaloids were isolated from this fraction. Compound AP-1 has good activity against LCSCs(P<0.01)with IC50 value(3.84±0.12) μmol/L. Conclusion AP-1 isolated from the sponge Aaptos aaptos exhibited significant activity against LCSCs. |
| keywords:aaptamine alkaloid lung cancer stem cell proliferation AP-1 |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
| 关闭 |
