聚乙二醇-伊立替康对裸鼠人乳腺癌移瘤模型的药效学研究  

Pharmacodynamic study of polyethylene glycol irinotecan on the xenograft tumor model of human breast cancer in nude mice

作　　者：王强[1] 张祖兵 王平[1] 田媛[1] 唐春艳[1] 刘玉川[1] 程强[1] 孙文霞[1] 

机构地区：[1]成都大学,四川抗菌素工业研究所,抗生素药效评价中心,成都610052 [2]成都一平医药科技发展有限公司,成都610041

出　　处：《药物分析杂志》2017年第1期83-89,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:评价长效拓扑异构酶Ⅰ抑制剂聚乙二醇-伊立替康(YP-pegol)的体内抗肿瘤活性。方法:将体外传代培养后的人乳腺癌MCF-7细胞接种到裸鼠右前肢腋部皮下,建立裸鼠人乳腺癌移植瘤模型。待肿瘤体积增长至满足试验要求后,将裸鼠按肿瘤体积随机分为6个组即4个YP-pegol剂量组,1个溶媒对照组和1个阳性对照组。每4天给药1次,共给药3次。每周测量裸鼠体重和瘤体积2~3次。计算出相对肿瘤体积(RTV)、相对肿瘤增殖率(T/C),并使用SPSS 13.0统计软件对各组动物体重、肿瘤体积结果进行统计学处理。疗效评价标准:T/C>40%为无效;T/C≤40%,并经方差分析与阴性对照组比较,P<0.05表示有效并具有统计学意义;用单因素方差分析的方法比较各组动物体重数据,以P<0.05表示有统计学意义;在毒性相当(动物死亡率和体重下降相当)的情况下,对供试品组和阳性对照组的T/C进行比较。结果:YP-pegol各剂量组和阳性对照组的体重均值与溶媒对照组的体重数据均值无显著差异,YPpegol对裸鼠体重无明显影响;给药后第26天,供试品YP-pegol 20、40、60、90 mg·kg^(-1)剂量组、阳性对照组(伊立替康,60 mg·kg^(-1))与溶媒对照组比较,瘤体积(RTV)明显小于溶媒对照组(P<0.05),并且各治疗组的T/C<40%;与阳性对照组比较,YP-pegol高剂量组(90 mg·kg^(-1))肿瘤体积明显低于阳性对照组(P<0.05)。给药后第62天,YP-pegol次高、高剂量组的相对肿瘤体积(RTV)与阳性对照组比较,明显低于阳性对照组(P<0.05)。结论:YP-pegol对裸鼠人乳腺癌移植瘤具有明显的抑瘤作用并呈现一定的量效关系;YP-pegol较注射用伊立替康具有更好的疗效。Objective： To assess the antitumor activity and safety of the long-acting topoisomerase I inhibitor polyethylene glycol-irinotecan （ YP-pegol ） using nude mice models of xenograft human breast cancer. Methods： The in vitro cultured human breast cancer cell MCF-7 was inoculated into the subcutaneous of tile right forelimb axillary in nude mice to establish the xenograft model of human breast cancer. When the tumor volume met the test requirements, the eligible nude mice were randomly assigned to six groups according to the tumor volume： four YP-pegol close groups （ 20,40, 60, 90 mg·kg-1 ）, a solvent control group and a positive control group （ irinotecan 60 mg·kg-1 ）. The drugs were administered every 4 days for a total of 3 times. The body weight and tumor volume of the mice was measured 2-3 times weekly. The relative tumor volume （ RTV ） and relative tumor proliferation rate （ T/C, % ） were calculated according to the formula. Comparing the YP-pegol groups with the solvent control group through the statistical analysis of body weight, RTV and T/C. The body weights and tumor volumes of the six groups were analyzed with SPSS for Windows 13.0 statistical software. Curative effect evaluation standard： if TIC 〉 40%, invalid; if TIC ≤40%, and compared with the solvent control group by variance analysis, P 〈 0.05 indicated that the YP-pegol therapy for xenograft tumor mic, e models was effective and there was statistical significance. The body weight data were compared with single factor analysis of variance, and the P 〈 0.05 indicated that there was statistically significant ; if the toxicities were comparable （ The mortality and weight decreasing were comparable ）, then the T/C of the test group was compared with the positive control group. Results： The results of weight decreasing in the 6 groups were comparable, and YP-pegol had no significant effec, t on the weight changes of the model mice; 26 days after the first administration, the YP-pegol groups and the positive con

关 键 词：聚乙二醇-伊立替康 拓扑异构酶Ⅰ抑制剂 人乳腺癌 移植瘤模型 抗肿瘤 活性分析 

分 类 号：R917[医药卫生—药物分析学]