新抗肿瘤抗生素NC0604的研究.docVIP

新抗肿瘤抗生素NC0604的研究 陈彩霞，何琪杨，司书毅，许鸿章*，鲁敏，解云英，陈汝贤*（中国医学科学院 中国协和医科大学医药生物技术研究所，北京，100050） 摘要：目的 对新抗肿瘤抗生素NC0604进行分离、纯化、结构鉴定，并对其生物活性、肺毒性进行检测，以寻找抗肿瘤作用更好而肺毒性更低的博莱霉素类抗肿瘤抗生素。方法 从轮枝链霉菌平阳变种（Streptomyces verticillus var. Pingyangensis n.sp）发酵产生的复合物中分离、纯化，得到抗生素NC0604，并通过各种光谱分析确证其化学结构；采用MTT法检测了其体外抗肿瘤活性；根据病理组织学观察和羟脯氨酸(HYP)含量检测对其肺毒性进行了评价。结果 NC0604具有博莱霉素族母核结构，其末端胺体为amidepropyl spermidine即[-NH（CH2）3NH（CH2）4NHCH2CH2CONH20.01）；根据T Ashcroft[1]的方法，判断NC0604组小鼠肺纤维化程度为2~3级，而博莱霉素组为6～7级。结论 新抗生素NC0604为一属于博莱霉素族的新化合物，与博莱霉素相比，具有更好的生物活性和更低的肺毒性。 关键词：NC0604；结构测定；抗肿瘤活性；肺毒性；博莱霉素 Studies on a new antitumor antibiotic NC0604 CHEN Caixia，HE Qiyang, SI Shuyi, XU Hongzhang*, LU Min, XIE Yunying, CHEN Ruxian* (Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences Peking Union Medical College ,Beijing,100050) ABSTRACT: OBJECTIVE To isolate and purify the new antibiotic NC0604，determine its structure and detect the bioactivity and pulmonary toxicity in order to find a new antibiotic of bleomycin group with better antitumor activity and lower pulmonary toxity. METHODS NC0604 was isolated from an active complex produced by Streptomyces verticillus var. Pingyangensis n.sp. and the structure was determined by spectral analysis. It’s antitumor activity in vitro was determined with MTT assay. The status of pulmonary toxicity was evaluated by determining the content of hydroxyproline(HYP) and observing the histomorphological changes of the lung tissues on day 28 after NC0604 administration. RESULTS NC0604 contains mother nuclide of bleomycins and amidepropyl spermidine as the terminal amine moiety. It was highly active against human HepG2、MCF7、MCF7/DOX、KB、HCT116 and BGC cells with antitumor activity 3~9 times that of bleomycin. The content of HYP in the lung tissues treated with NC0604 was lower than those treated with bleomycin （P0.01）. According to T Ashcroft[1] method, the status of pulmonary fibrosis by NC0604 and bleomycin was measured microscopically as grade 2~3 and 6~7 respectively. CONCL