^(125)IUdR对裸鼠原位膀胱癌的治疗作用  

The experimental study of ^(125)IUdR therapy in nude mice bearing orthotopic bladder cancer

作　　者：侯建全[1] 吴光[1] 何军[2] 温端改[1] 

机构地区：[1]苏州大学附属第一医院泌尿外科,215006 [2]苏州大学附属第一医院,江苏省血液研究所

出　　处：《中华实验外科杂志》2007年第10期1231-1233,共3页Chinese Journal of Experimental Surgery

基　　金：江苏省135重点人才资助项目(RC2003094);江苏省高校科研基金资助(Q1122031);江苏省社会发展基金(BS2005610);江苏省卫生厅科技基金(H200517);江苏省六大高峰项目(06-B-021)

摘　　要：目的观察膀胱内灌注^(125)I-脱氧尿嘧啶核苷(^(125)IUdR)对裸鼠原位膀胱癌治疗作用。方法建立裸鼠原位膀胱癌模型,设立对照组、MMC组、^(125)IUdR组和联合组。对照组不予任何处理,MMC组、^(125)IUdR组和联合组分别予膀胱灌注1g/L的丝裂霉素(MMC)0.1 ml、18.5 kBq/10μl的^(125)IUdR 0.1 ml和18.5 kBq/10μl的^(125)IUdR 0.1 ml联合腹腔注射氨甲喋呤(MTX)(注射量为20 mg/kg体重)治疗。通过流式细胞仪(FCM)分析、病理学检查、Caspase-3检测和生存分析比较各组的治疗情况。结果MMC组、^(125)IUdR组和联合组裸鼠的平均膀胱肿瘤重量均明显小于对照组,抑瘤率分别为33.45%、31.46%和50.27%;^(125)IUdR组和联合组肿瘤细胞的S期百分比低于对照组[分别为(3.9±0.7)%和(0.18±0.03)%,而凋亡指数明显高于对照组[分别为(3.367±1.629)%和(25.767±11.875)%;Caspase-3检测三个治疗组凋亡细胞数(评分分别为4.67、4.67和9分)多于对照组(评分为1.33分);三个治疗组裸鼠的平均生存时间(分别为35.33、36.67、44.67 d)较对照组(为29.33 d)延长。结论膀胱内灌注^(125)IUdR对裸鼠原位膀胱癌的治疗安全有效;^(125)IUdR能选择性的杀伤DNA合成期S期的肿瘤细胞,显著抑制膀胱癌细胞的增殖,干扰膀胱癌细胞的DNA合成,延长实验裸鼠的生存期;氨甲喋呤联合^(125)IUdR具有协同效应,可增强疗效。To investigate the efficacy and feasibility of intravesical instillation of 5-[ ^125IUdR] iodo-2＇ -deoxyuridine （^125IUdR） in the treatment of orthtopic bladder cancer. Methods The model of orthotopic bladder cancer was established on BALB/nu/nu mice. The nude mice bearing orthotopic bladder cancer were randomly assigned to 4 groups ： control group, MMC group, ^125IUdR group and combined group. The nude mice bearing orthotopic bladder cancer in each group were administered with nothing, 1 g/L MMC 0. 1 mL, 18.5 kBq/10 p.1 ^125IUdR 0.1 mi and 18.5 kBq/10 /.d ^125IUdR 0. 1 mi combined with methotrexate （MTX） by intraperitoneal injection separately. The therapeutic effect in each group was compared through flow cytometry （FCM） .pathological examination, caspase-3 and survival analysis. Results The bladder weight of mice bearing orthotopic bladder tumor was significantly lighter in MMC group,^125IUdR group and combined group than in control group, and the inhibitory rate in in MMC group ,^125IUdR group and combined group was 33.45% , 31.46% and 50.27% respectively. The Sphase percentage of tumor cells in 125IUdR group and combined group was significantly lower than in therapeutic group [ （3.9± 0.7 ）% and （0.18 ± 0.03 ）% separately] than in control group, on the other hand apoptotic index of tumor cell was obviously higher [ （3. 367±＋ 1. 629） % and （25. 767 ± 11. 875 ） % separately ] than the latter. The analysis of caspase-3 display that apoptosis cells were obviously higher in therapeutic group than in control group. The survival time of mice bearing orthotopic bladder cancer were much lon- ger in therapeutic group （35.33 d,36.67 d and 44.67 d separately） than in control group （29.33 d）. Condusion ^125IUdR can selectively kill S-phase tumor cells, suppressed tumor cell proliferation, obstructed the DNA synthesis of tumor cell and extended the survival of orthotopic tumor-bearing mice. The combination of ^125IUdR and MTX showed synergistic effect and enhanced therapeutic e

关 键 词：脱氧尿嘧啶核苷 膀胱癌 氨甲喋呤 疗效 

分 类 号：R737.14[医药卫生—肿瘤]