从嗜线虫杆菌分离的吲哚衍生物抗肿瘤活性的研究

Study on the anti-tumor activity of an indole derivative isolated from Xenorhabdus

目的 :研究嗜线虫杆菌次级代谢产物吲哚衍生物的抗肿瘤活性。方法 :用有机溶剂萃取和硅胶柱层析对嗜线虫杆菌发酵液进行提取和分离 ,获得吲哚衍生物 ,用MTT法测定其体外杀肿瘤细胞作用 ,利用裸鼠接种人HeLa细胞模型检测其体内抗肿瘤活性。结果 :从发酵液粗提物中分离得到 5个组分 ,从有抗肿瘤活性的组分中再分离得到化合物 3 吲哚乙基 (3’ 甲基 2’ 酮 )戊酰胺 ,其对HepG2 ,HeLa,HT 2 9,BGC 82 3和K5 6 2的IC50 分别为(0 .12± 0 .0 1) ,(1.83± 0 .0 2 ) ,(6 .16± 0 .5 2 ) ,(1.4 5± 0 .12 ) ,(5 .90± 1.17) μg·mL-1,对正常人肺成纤维细胞MRC 5和正常人肝细胞L 0 2生长的影响很小。接种HeLa肿瘤细胞裸鼠连续灌服上述吲哚衍生物 (2 ,4和 8mg·kg-1) 7d ,抑瘤率分别为 4 8.1% ,5 6 .5 %和 72 .2 %。结论 :嗜线虫杆菌发酵液来源的 3 吲哚乙基 (3’ 甲基 2’ 酮 )戊酰胺具有较强的抗肿瘤活性。

Objective:To investigate the anti tumor activity of the indole derivative isolated from fermentation broth of Xenorhabdus .Methods:The broths were extracted with ethyl acetate and concentrated. The crude extracts were refined on columns of silica gel.The in vitro anti tumor activity of fractions and compounds obtained were tested using MTT assay. The in vivo anti tumor activity of compound were performed on Balb/c nude mice inoculated intradermally in the back with HepG2 cell.Nude mice bearing liver cacinoma were treated ig with saline,tested compound(2,4 and 8mg·kg -1 ) for 7 days and ip with cisplantin(8mg·kg -1 ) for 5 days respectively.Results:Two fractions from Xenorhabdus nematophilus B1 were found to have potential anti tumor activity,and the frections were rechromatographed on a silica gel.Compound 3 indoleethyl(3' methyl 2' oxo) valeramide was isolated on eluting with chloroform.The IC 50 of the compound obtained for HepG2,HeLa,HT 29,BGC 823 and K562 approximate to(0.12± 0.01), (1.83±0.02),(6.16±0.52),(1.45±0.12) and (5.90±1.17)μg·mL -1 ,respectively.The compound has little effect on the proliferation of normal human cells(MRC 5,L 02).The administration of 3 indoleethyl(3' methyl 2' oxo) valeramide resulted in dose dependent inhibition of tumor growth.Conclusion:3 indoleethyl (3' methyl 2' oxo) valeramide isolated from fermentation broth of Xenorhabdus has strong anti tumor activity.