注射用紫杉醇胶束体内抗肿瘤作用  

Anti-tumor effects of paclitaxel micelle for injection in vivo

作　　者：周国亮[1] 韩滨[1] 宋翼升[1] 孙菁[2] 周劲松 蒋新国[2] 李端[2] 宣尧仙[1] 

机构地区：[1]浙江省医学科学院安全性评价研究中心,浙江杭州310052 [2]复旦大学药学院,上海201203 [3]上海谊众生物技术有限公司,上海200237

出　　处：《中国新药与临床杂志》2014年第8期582-587,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：浙江省自然科学基金项目(LY13H160031);浙江省卫生厅项目(2012RCB008);浙江省科学技术厅项目(2013F20005);浙江省中医药管理局项目(2014ZA016)

摘　　要：目的观察注射用紫杉醇胶束对荷人结肠癌HT29或人肺腺癌A549移植瘤裸小鼠的治疗效果。方法将已在裸小鼠体内传三代的人结肠癌HT29或人肺腺癌A549组织块接种在雄性Balb/c裸小鼠前肢腋皮下,待瘤体长至100 mm3左右,挑选合适的小鼠分成阴性对照组、空白胶束组、紫杉醇注射液对照组、紫杉醇胶束组（10、20、50 mg·kg^-1）等6组,每组6只裸鼠。各组每3日经尾静脉注射给药1次,共给7或8次,其中紫杉醇胶束50 mg·kg^-1组给药4次。给药期间观察裸小鼠的一般反应,每次给药前称裸小鼠体重并测量肿瘤大小,计算相对肿瘤体积（RTV）、相对肿瘤增殖率（T/C）。结果在HT29人结肠癌和A549人肺腺癌模型实验中,仅紫杉醇胶束50 mg·kg^-1组在给药4次后裸小鼠出现消瘦、反应迟钝、活动减少、皮肤光泽较差、稀便等反应,体重明显减轻（与阴性对照组相比,P〈0.05或P〈0.01）,但未出现动物死亡;其他各组小鼠未出现明显的异常反应。两模型实验中紫杉醇胶束20、50 mg·kg^-1在第2～4次给药后RTV明显小于阴性对照组（P〈0.01）,T/C小于40%（P〈0.01）。紫杉醇胶束10 mg·kg^-1组和空白胶束组的T/C大于40%,RTV与阴性对照组比较无显著差异（P〉0.05）。结论紫杉醇胶束20、50 mg·kg^-1可显著抑制荷HT29人结肠癌和A549人肺腺癌裸小鼠移植瘤的生长,但是紫杉醇胶束50 mg·kg^-1系统毒性明显高于20 mg·kg^-1。AIM To study anti-tumor effects of paclitaxel micelle （PTX-PM） for injection on tumor- bearing mice in vivo. METHODS Male nude mice were implanted with xenograft fragments of human lung adenocarcinoma A549 or human colorectal cancer HT29 tissue subcutaneously in the right flank. When tumor in the nude mice reached a tumor volume of 100 mm^3, the nude mice bearing tumor were divided into 6 groups （control, polymeric micelle （PM）, paclitaxel injection （PTXI）, three PTX-PM treated groups）. Each group had 6 mice. A single dose of PTX-PM in saline was administered intravenously at 10, 20 mg·kg^-1 every three days. PTXI in saline was also administered intravenously at 20 mg· kg^-1 every three days, 7 - 8 times in the experiment. While in the PTX-PM 50 mg·kg^-1 group only 4 times were given. In control experiments, saline and PM vehicle were used. Tumor size and body weight was measured before every time for the duration of the study, and tumor volume, relative tumor volume or relative proliferation rate of tumor was calculated. RESULTS None of the animals treated with PTX-PM died in the two model experiments during the experimental period. Only the tumor-bearing mice in the FFX-PM 50 mg·kg^-1 group appeared response slowing, activity decreasing, poor skin luster, loose stools and body weight losing （P 〈 0.05 or P 〈 0.01） after administered 4 times. There were no obviously abnormal reactions in the mice of the 10 or 20 mg·kg^-1 group. In the PTX-PM 20 or 50 mg·kg^-1 group of the two model experiments, the relative tumor proliferation rates were less than 40% and the relative tumor volumes were significant different from the control group till the end of the experiment. While in the PTX-PM 10 mg·kg^-1 group or PM group the relative tumor proliferation rates were greater than 40% and the relative tumor volumes were similar to the control group. CONCLUSION Under the experimental conditions, PTX-PM 20 or 50 mg·kg^-1 could inhibit HT29 and A549 xenografts growth in nude mice, and had a signifi

关 键 词：紫杉醇 抗肿瘤药 给药系统 纳米复合物 

分 类 号：R927.2[医药卫生—药学] R979.1