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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 evaluate the in vivo antitumor activity of long-acting topoisomerase I inhibitor polyethylene glycol-irinotecan (YP-pegol). Methods: Human breast cancer MCF-7 cells were inoculated subcutaneously into the axilla of the right forelimb in nude mice and the model of human breast cancer xenografts was established. After the tumor volume increased to meet the test requirements, the nude mice were randomly divided into 6 groups according to the tumor volume, namely 4 YP-pegol dose groups, 1 vehicle control group and 1 positive control group. Administered once every 4 days for a total of 3 doses. Body weight and tumor volume of nude mice were measured 2 to 3 times weekly. The relative tumor volume (RTV) and the relative tumor growth rate (T / C) were calculated. SPSS 13.0 statistical software was used to calculate the body weight and tumor volume of each group. Efficacy evaluation criteria: T / C> 40% is invalid; T / C≤40%, and by ANOVA compared with the negative control group, P <0.05 is valid and statistically significant; by one-way ANOVA Group body weight data with statistical significance at P <0.05; T / C with test group and positive control group at comparable toxicities (comparable animal mortality and weight loss). Results: There was no significant difference between the mean body weight of YP-pegol groups and the positive control group and the body weight data of the vehicle control group. YPpegol had no significant effect on body weight of nude mice. On the 26th day after administration, the YP-pegol 20 , 40,60 and 90 mg · kg -1, and the positive control group (irinotecan, 60 mg · kg -1) compared with the vehicle control group, the tumor volume (RTV) was significantly lower than the vehicle control (P <0.05), and the T / C of each treatment group was less than 40%. Compared with the positive control group, the volume of tumor of YP-pegol high dose group (90 mg · kg -1) was significantly lower than that of the positive control group (P <0.05). On the 62nd day after administration, the relative tumor volume (RTV) of YP-pegol sub-high and high dose groups was significantly lower than that of the positive control group (P <0.05). CONCLUSION: YP-pegol has obvious anti-tumor effect on human breast cancer xenografts in nude mice and shows a dose-effect relationship. YP-pegol has better efficacy than irinotecan for injection.