目的通过对BALB/C小鼠原位结肠癌实验模型应用5’-脱氧氟尿苷治疗,并同传统抗癌药物5-氟尿嘧啶进行比较,观察分析5’-脱氧氟尿苷在动物体内抗结肠癌细胞效应及在组织和血液中的转化。方法60只BALB/C小鼠采用盲肠原位瘤块接种法建立小鼠结肠癌CT26实验模型,术后第3天开始用随机数字表法把小鼠分成3组,每组20只。根据体重分别连续5d腹腔注射:(1)5’-脱氧氟尿苷组:5’-脱氧氟尿苷0.1mg/g;(2)5-FU组:5-FU0.02mg/g;(3)对照组:0.9%氯化钠溶液0.4mL。每组分别于术后第2、3周处死6只小鼠,测量肿瘤重量和体重变化,检测血常规和肝肾功能,并各保留8只小鼠等待自然死亡记录带瘤生存时间。另外把14只小鼠皮下接种CT26细胞约2周后,待注射局部形成皮下肿物,用随机数字表法分成2组,每组各7只,分别腹腔注射5’-脱氧氟尿苷0.1mg/g和5-氟尿嘧啶0.02mg/g,15min后同时处死取血和肿瘤组织测定转化后的5-氟尿嘧啶含量。结果5’-脱氧氟尿苷组小鼠肿瘤重量最小,术后2周和3周平均重量分别为(0.07±0.12)g和(0.24±0.29)g;平均带瘤生存期为(32.6±8.9)d。5-氟尿嘧啶组术后2周和3周平均肿瘤重量分别为(0.74±0.43)g和(1.13±0.75)g,平均带瘤生存期为(22.8±5.9)d。对照组术后2周和3周平均肿瘤重量分别为(0.70±0.47)g和(1.93±0.83)g,平均带瘤生存期为(17.5±2.8)d。5’-脱氧氟尿苷组小鼠肿瘤重量、带瘤生存期与5-氟尿嘧啶组及对照组相比差异具有统计学意义(P〈0.05)。各组小鼠在WBC、Hb、Plt、肝肾功能方面差异无统计学意义(P〉0.05),但5-氟尿嘧啶组在手术及应用药物后体重下降比较明显,与5’-脱氧氟尿苷组及对照组相比差异具有统计学意义(P〈0.01)。5’-脱氧氟尿苷组小鼠在注药15min
Objective To evaluate the anticancer activity of 5'-dexoxy-fluorouridine on colon cancer experimental models in BALB/C mice, compared with 5'-fluorouraeil, an anticancer agent widely used in clinic, meanwhile, examined the conversion of 5' - Dexoxy-fluorouridine to 5' -fluorouracil in cancer tissues and serum of mouse models. Methods The xenografts of mouse colon cancer cell line CT 26 were trans- plantated to cecum in 60 male BALB/C mice. Three days lated, these mice were divided into 3 groups and intro- peritoneally injected : (1) 5' - dexoxy- fluorouridine 0.1 rag/g, (2) 5' - Fluorouracil 0.02 mg/g, (3) 0.9% sodium chloride 0.4 mL (as a control) , respectively. Two and three weeks later, 6 mice were sacri- ficed in every group respectively to measure the weight of tumors and bodies, to examine the Hb, RBC, WBC, PLT, AST, ALT, UREA, and CREA in blood. The rest 8 mice in each group were fed generally, and the survival time from operation to natural death was recorded. In addition, 14 mice with xenografts of CT 26 about 2 weeks, were divided into 2 groups averagely, 5' -dexoxy-fluorouridine 0.1 mg/g and 5' -flu- orouracil 0.02 mg/g were intro-peritoneally injected respectively. Fifteen rain later, the converted 5 ' -flu- orouracil was detected from the blood and tumor tissues in sacrificed mice. Results The lest tumor average weight was found in the mice injected 5'-dexoxy-fluorouridine, being (0.07±0. 12) g and (0.24g±0.29) g for the mice sacrificed at 2 and 3 weeks later, respectively. The average survival time for rest mice was (32.6±8.9) d. The average tumor weight in 5' - fluorouracil group was (0.74±0.43) g and (1.13±0.75) g at 2 and 3 weeks later, and the average survival time for the rest was (22.8±5.9) d, respectively. The average tumor weight in the control group was (0.70±0.47) g and (1.93±0.83) g at 2 and 3 weeks, and the average survival time for the rest was (17.5±2.8) d. Either the average tumor weight or average s