舒尼替尼衍生物ZH26体内外抗肿瘤作用  

Anti-tumor efficacy of sunitinib derivative:ZH26

作　　者：肖璘[1] 刘珉宇[2] 蔡立[1] 郑红艳[1] 邓轶方[1] 赵小烨 刘全海[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200437 [2]上海交通大学药学院,上海230032 [3]新昌制药厂,浙江312500

出　　处：《世界临床药物》2012年第5期275-280,共6页World Clinical Drug

基　　金：上海市科委生物医药重点科技攻关项目;课题编号:09431901400

摘　　要：目的研究舒尼替尼衍生物ZH26的抗肿瘤作用。方法采用甲基噻唑比色法体外检测ZH26对多种肿瘤细胞株的生长抑制作用;建立S180肉瘤、Colon26结肠癌小鼠肿瘤模型和裸鼠人体肿瘤移植瘤NCI-H460人大细胞肺癌移植瘤、SPC-1肺腺癌移植瘤模型,评价ZH26的体内抗肿瘤活性。结果 ZH26体外对多株肿瘤细胞株有较好的抑制作用,对大多数肿瘤细胞株的IC50值为3.33～5.68μg/mL,与舒尼替尼相当。体内试验表明,30～90 mg/kg ZH26对小鼠S180肉瘤的抑瘤率为40.55%～66.82%;对小鼠Colon26结肠癌的抑瘤率为55.41%～78.14%;对NCI-H460人大细胞肺癌的抑瘤率为48.14%～70.56%;对SPC-1肺腺癌的抑瘤率为42.06%～92.18%。结论 ZH26具有良好的体内外抗肿瘤作用,相关机制尚待进一步研究。Objective To study the anti-tumor efficacy of sunitinib derivative,ZH26,in vitro and in vivo.Methods The efficacy in vitro of ZH26 was detected by MTT assay in several cell lines.The efficacy in vivo evaluated with inhibitory ratio of tumor size was tested by mouse tumor models,such as S180 and Colon26 mice models,and human cancer xenograft models,including NCI-H460 and SPC-1.Results There was significant effect of ZH26 for growth inhibitory against tumor cell lines with the IC50 values range from 3.33～5.68 μg/mL;AS ZH26 dose within 30～90 mg/kg the inhibitory ratios were 40.55%～66.82% in mouse S180 tumor model and 55.41%～78.14% in mouse Colon26 tumor model;The data display anti-tumor efficacy of ZH26 with inhibitory ratios of 48.14%～70.56% and 42.06%～92.18% in human cancer NCI-H460 and SPC-1 mice models.Conclusion ZH26 has good anti-tumor efficacy in vitro and in vivo.

关 键 词：ZH26 抗肿瘤 舒尼替尼 舒尼替尼衍生物 

分 类 号：R979.1[医药卫生—药品]