Xenorhabdus和Photorhabdus代谢产物体外抗肿瘤活性

THE ANTI-TUMOR ACTIVITY OF METABOLITES FROM XENORHABDUS AND PHOTORHABDUS IN VITRO

用 8株昆虫病原线虫共生菌 (Xenorhabdus属和Photorhabdus属 )的发酵液进行了体外抗肿瘤活性的研究 ,从中筛选出活性较高的菌株 -嗜线虫致病杆菌 (XenorhabdusnematophilaCB6 )。经有机溶剂萃取和硅胶柱层析对嗜线虫致病杆菌发酵液进行进一步分离 ,得到 5个组分。用MTT法测定体外杀肿瘤细胞作用 ,发现其中 2个组分具有抗肿瘤活性。组分 3对HepG2、Hela、BGC 82 3、A 5 4 9、K5 6 2和HT 2 9的IC50 分别等于 3 1μg/ml、8 5 μg/ml、2 1μg/ml、3 0 μg/ml、4 4 μg/ml和 1 5 μg/ml;组分 5对HepG2、Hela、BGC 82 3、A 5 4 9、K5 6 2和HT 2 9的IC50 分别等于 0 1μg/ml、1 8μg/ml、0 1μg/ml、0 4 μg/ml、1 2 μg/ml和 0 6 μg/ml。同时发现抗肿瘤活性组分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。该研究在国内率先报道了嗜线虫致病杆菌发酵液具有较强抗肿瘤活性 ,为新药物的研制和开发提供了一条崭新的途径。

Eight strains of Xenorhabdus and Photorhabdus were isolated from nematodes of the Steinernema and Heterorhabdus.The supernatants of their fermentation filtrates were extracted with EtOAc and their anti-tumor activities were tested using MTT(Microculture tetrazolium test)bioassay.Xenorhabdus nematophila strain CB6 was the best performance for anti-tumor activity among eight strains.The crude extracation of strain CB6 was separated further with a column of silica gel.Five fractions were obtained. Two fractions have higher anti-tumor activity. IC 50 of fraction 3 for HepG2、Hela、BGC-823、A-549、K562 and HT-29 was 3.1 μg/ml, 8.5 μg/ml, 2.1 μg/ml, 3.0 μg/ml, 4.4 μg/ml and 1.5 μg/ml respectively. IC 50 of fraction 5 for HepG2, Hela, BGC-823, A-549, K562 and HT-29 was 0.1 μg/ml, 1.8 μg/ml, 0.1 μg/ml, 0.4 μg/ml, 1.2 μg/ml and 0.6 μg/ml respectively. The two fractions almost have no effect on the proliferation of human normal cells. The anti-tumor activity of Xenorhabdus was reported for the first time in China. This research may provide a new way for development of new anti-tumer drug.