小剂量环磷酰胺治愈荷膀胱癌小鼠动物模型的建立

Experimental study on establishing mouse model of BTT739 tumor-bearing mice cured by a low dose of CTX

关键词:  环磷酰胺  小剂量化疗  动物模型  小鼠膀胱癌  T739小鼠

Key words:  cyclophosphamide  a low dose of chemotherapy  animal model  bladder carcinoma  T739 mice

摘要:

［目的］建立单一剂量环磷酰胺(cyclophosphamide，CTX)治愈荷膀胱癌小鼠的动物模型。［方法］T739小鼠皮下接种小鼠可移植性膀胱移行细胞癌组织建立荷瘤小鼠模型。肿瘤接种后第7天，不同剂量的CTX单次腹腔内注射，观察荷瘤小鼠用药后体重和肿瘤结节直径的变化，找出CTX可治愈多数荷瘤小鼠的最低有效剂量。然后再取12只荷瘤T739小鼠随机分成两组，最低有效剂量的CTX单次腹腔内注射，等量生理盐水作对照，分别在治疗后第4、14天内眦静脉取血进行白细胞计数。［结果］接种2 mm³ 的小鼠膀胱癌肿瘤组织可使T739小鼠肿瘤进行性生长，接种后第7天肿瘤直径约为2～4 mm。15 ～400 mg/kg的CTX单次腹腔内注射后1周内，荷瘤小鼠肿瘤结节缩小的速率和毒性反应均与所用CTX的剂量呈正相关。CTX治疗后2月，100 ～200 mg/kg CTX治疗组的荷瘤小鼠全部死亡；40 mg/kg CTX治疗后20%的荷瘤小鼠存活；15 mg/kg CTX治疗组60%的荷瘤小鼠存活，与对照组比较差异具有统计学意义(P<0.01)。15 mg/kg CTX治疗后第4天荷瘤小鼠外周血WBC为(11.36±0.30)×10⁹/L，对照组为(11.14±2.14)×109/L，两组数据比较差异无统计学意义(P>0.05)；治疗后第14天，治疗组小鼠WBC计数降为(8.46 ± 0.76)×10⁹/L，与CTX治疗后第4天WBC计数比较差异具有统计学意义(P<0.05)，但与对照组(9.86±3.40)×109/L比较差异无统计学意义(P>0.05)。［结论］15 mg/kg CTX单次腹腔内注射后荷瘤小鼠无明显毒性反应，并可使多数荷瘤小鼠肿瘤治愈，因此，小剂量CTX治愈荷膀胱癌小鼠模型成功建立。

Abstract:

［Objective］To establish an animal model of BTT739 mice cured by a single dose of cyclophosphamide (CTX).［Methods］Mouse bladder carcinoma tissue was inoculated subcutaneously into BTT739 mice. 7 days later, different doses of CTX were used intraperitoneally to treat these tumor-bearing mice. Tumor sizes and body weight were observed and recorded subsequently, and the minimal effective dose of CTX that could cure most of the tumor-bearing mice was found. Then another 12 tumor-bearing mice were randomly divided into two groups: the minimal effective dose of CTX was given intraperitoneally and the same volume of NS as control. The WBC count was measured at the 4th and 14th days after treatment.［Results］Inoculation of 2 mm³ bladder carcinoma tissue could make tumor cell progressive growth in T739 mice. The tumor sizes were 2～4 mm on day 7 after inoculation. Within 1 w after 15 ～400 mg/kg CTX treatment, the speed of tumor shrinkage and the side effects of tumor-bearing mice had a positive relationship with the dose of CTX used. 2 months after CTX treatment, no mice was alive in 100～400 mg/kg CTX group; 20% of mice were alive in 40 mg/kg CTX group; 60% of mice were alive in 15 mg/kg CTX group. There was significantly difference between 15 mg/kg CTX group and control group (P<0.01). On the 4th day after treatment, there was no significantly difference in peripheral blood WBC count in tumor-bearing mice between 15 mg/kg CTX group (11.36±0.30)×10⁹/L and control group (11.14±2.14)×10⁹/L (P>0.05). The WBC count decreased to (8.46±0.76)×109/L in mice of CTX group on the 14th day after treatment. There was significantly difference in WBC count of the mice between the 4th and the 14th day after CTX treatment (P<0.05); but there is no significantly difference compared with control group (9.86±3.40)×109/L (P>0.05).［Conclusions］A single dose of CTX (15 mg/kg) had no obvious side effects, but could cure most of these tumor-bearing T739 mice. The animal model cured by a low dose of CTX (15 mg/kg) had been established successfully in BTT739 tumor-bearing mice.