1种阿霉素新型前体药物的抗肿瘤活性作用研究  

Evidence of a prodrug of doxorubicin in antitumor activity in vitro

作　　者：刘晓[1] 邵方元[1] 田旭岩[1] 肖满珊 陈宏远[1] 

机构地区：[1]广东药学院基础学院病原生物学与免疫学系,广东广州510006

出　　处：《广东药学院学报》2014年第1期81-84,共4页Academic Journal of Guangdong College of Pharmacy

基　　金：广州市科学研究专项入库项目(148);中山市科技局项目(20101H021)

摘　　要：目的考察新合成目标前体药物N-苄氧羰基-丙氨酰-丙氨酰-天冬酰-阿霉素在体外对肿瘤细胞增殖的影响,建立合理的前体药物体外抗肿瘤的评价方法。方法分别采用MCF-7和Caski 2种肿瘤细胞株,前药处理48 h及72 h后,分别通过MTT法对常氧及低氧诱导培养的细胞进行检测。结果常氧培养条件下,测得目标前药对MCF-7和Caski细胞株的半数抑制浓度IC50分别大于(137.92±6.68)μmol/L和(25.3±4.12)μmol/L,其对2种细胞株的增殖抑制作用较原药分别降低了54倍及40倍以上。低氧诱导培养条件下,目标前药对Caski细胞株半数抑制浓度IC50为(12.6±4.30)μmol/L,其对Caski细胞株的增殖抑制作用较原药降低了49倍;而与常氧培养下相比,其对Caski细胞株的增殖抑制作用提高了2倍。结论 N-苄氧羰基-丙氨酰-丙氨酰-天冬酰-阿霉素与阿霉素相比对体外培养的肿瘤细胞增殖抑制作用明显降低,初步达到了通过化学修饰降低细胞毒性的作用。Objective To investigate the activity of a novel synthesis prodrug of doxorubicin in vitro and establish a method for evaluation of prodrug toxicity. Methods Two tumor cell lines Caski 2 and MCF-7 were cultured in the conventional normoxic and hypoxia-induced conditions respectively, and activities were detected by MTT assay when treated with prodrug atfter 48 and 72 hours. Results In the condition of normoxic culture, the 50% inhibitory concentration IC5o of the prodrug on MCF-7 and Caski ceils were higher than 137.92±6.68 μmol/L and 25.3±4.12 μmol/L,and the proliferation of both cells were reduced by more than 54 and 40 times. In the condition of hypoxia-induced culture, IC5o of Caski cells was 12.6±4.30 μmol/L, and the inhibition of proliferation reduced lower than 49 times, but raised 2 times compared with Caski normoxic condition. Conclusion The target prodrug has a remarkable lower inhibition of proliferation on cultured tumor cells than doxorubicin does, and the peptides chemical modification prodrug of doxorubicin may reduce its cytotoxicity side effects.

关 键 词：阿霉素 抗肿瘤 前体药物 

分 类 号：R979.1[医药卫生—药品]