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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。
Objective To observe the therapeutic effect of intravesical instillation of ~ (125) I-deoxyuridine (~ (125) IUdR) on orthotopic bladder cancer in nude mice. Methods The model of orthotopic bladder cancer in nude mice was established. The control group, MMC group, ~ (125) IUdR group and combination group were established. The control group received no intravesical instillation of 1 ml / ml mitomycin (MMC) 0.1 ml, 18.5 kBq / 10 μl of 125 IUdR 0.1 ml and 18.5 kBq / 10 μl of 125 IUdR 0.1 ml intraperitoneal injection of methotrexate (MTX) (injection volume of 20 mg / kg body weight) treatment. The treatment of each group was compared by flow cytometry (FCM) analysis, pathological examination, Caspase-3 test, and survival analysis. Results The mean bladder tumor weights of MMC group, ~ (125) IUdR group and combination group were significantly less than those of control group, and the tumor inhibition rates were 33.45%, 31.46% and 50.27%, respectively; The percentages of cells in S phase were lower than those in control group [(3.9 ± 0.7)% vs (0.18 ± 0.03)%, respectively) and were significantly higher than those in control group (3.367 ± 1.629% and 25.767 ± 11.875, %. The number of apoptotic cells in the three treatment groups (4.67, 4.67 and 9 respectively) was higher in Caspase-3 than in control group (score 1.33). The mean survival time of nude mice in three treatment groups was 35.33 , 36.67,44.67 d) than the control group (29.33 d). Conclusion Intravesical instillation of 125 IUdR is safe and effective for the treatment of orthotopic bladder cancer in nude mice. 125 IUdR can selectively kill tumor cells in the S phase of DNA synthesis, significantly inhibit the proliferation of bladder cancer cells and interfere with the bladder DNA synthesis of cancer cells prolongs the survival of experimental nude mice; methotrexate combined with ~ (125) IUdR has a synergistic effect and can enhance the efficacy.